Therapeutic agent for neurodegenerative diseases

Abstract

Provided are: an anti-gpNMB antibody that binds to gpNMB to act on the gpNMB and has properties including a property to remove dysfunctional microglia; and a use of the anti-gpNMB antibody. A humanized anti-gpNMB antibody according to the present invention binds specifically to at least one site in a region lying between a PMEL-CAF-like domain and a PKD domain of gpNMB.

Description

Treatment for neurodegenerative diseases The present invention relates to an anti-gpNMB antibody (especially a humanized antibody) having the activity of reducing the number of dysfunctional microglia, and / or the activity of removing amyloid β oligomers and / or phosphorylated tau and / or synuclein (α-synuclein, β-synuclein, γ-synuclein), and / or the activity of restoring the number of synapses, and / or the activity of suppressing or restoring decline in cognitive function and / or motor function, and to a pharmaceutical comprising a component having such activity. 1. Neurodegenerative diseases Neurodegenerative diseases are progressive neurological disorders in which toxic proteins (proteins that undergo structural changes, such as multimerization and aggregate formation, and are unable to be degraded within the cell) accumulate within neurons, impairing the neurotransmission and intracellular clearance functions of neurons, leading to neuronal death and resulting in cognitive decline, memory impairment, psychiatric disorders, and impaired motor function. There are no fundamental treatments for neurodegenerative diseases, and drugs are used to alleviate the symptoms associated with the disease. Most of these "neurodegenerative diseases" are "central neurodegenerative diseases." Diseases classified as neurodegenerative diseases include: (1) tauopathies (diseases in which neurodegeneration occurs mainly due to the accumulation of tau): specifically, Alzheimer's disease, frontotemporal lobar degeneration (FTLD-Tau), frontotemporal dementia (FTD), primary age-related tauopathy (PART), chronic traumatic encephalopathy (CTE), Pick's disease, corticobasal degeneration (CBD or CBS), progressive supranuclear palsy (PSP), and glioglobular tauopathy (GGT). , argyrophilic grain dementia (AGD) (argyrophilic grain disease), age-related tauastrogliotauopathy (ARTAG), familial British dementia (FBD), familial Danish dementia (FDD), FTDP17, multisystem tauopathy with dementia (MSTD), neurofibrillary tangle dementia, diffuse neurofibrillary tangle disease with calcification (DNTC), white matter tauopathy with globular glial inclusions (WMT-GGI), etc. (2) Neurodegenerative diseases other than tauopathies: Specific examples include Parkinson's disease (accumulation of α-synuclein, etc.), Huntington's disease (accumulation of mutant huntingtin, etc.), spinocerebellar degeneration (accumulation of polyglutamic acid proteins, etc.), hereditary spinocerebellar ataxia (accumulation of polyglutamic acid proteins, etc.), spinal-bulbar muscular atrophy (accumulation of polyglutamic acid proteins, etc.), dementia with Lewy bodies (accumulation of α-synuclein, etc.), Creutzfeldt-Jakob disease (accumulation of abnormal prion protein, β-synuclein, etc.), amyotrophic lateral sclerosis (ALS) (accumulation of SOD, TDP43, FUS (fused in sarcoma), α-synuclein, γ-synuclein, etc.), and frontotemporal lobar degeneration (FTLD-TDP, FTLD-FUS: accumulation of TDP43, FUS, etc.). 2. Alzheimer's disease (Alzheimer's type dementia) Dementia is recognized as a major problem amid the global trend toward an aging population. According to a survey conducted by Alzheimer's International, the number of people with dementia worldwide is expected to reach approximately 76 million in 2030, and then increase to 139 million in 2050. According to the World Health Organization (WHO), approximately 60-70% of dementia cases are reported to be Alzheimer's disease (https: / / www.who.int / news-room / fact-sheets / detail / dementia). Two major pathologies have been reported for Alzheimer's disease: senile plaques (amyloid deposits) and neurofibrillary tangles (tau accumulation). Because familial Alzheimer's disease patients have genetic mutations involved in increased amyloid production, research is underway into antibodies and vaccines against amyloid beta (Aβ), a component of amyloid. Various anti-Aβ antibodies that remove amyloid deposits (Non-Patent Document 1) and drugs that target highly toxic Aβ oligomers (Non-Patent Document 2) have already been clinically developed, and lecanemab (Non-Patent Document 3, Non-Patent Document 72) was approved by the FDA in 2023. However, it has been reported that the effectiveness of these drugs targeting amyloid is limited and there is a high risk of side effects. Meanwhile, tau, another component of neurofibrillary tangles, has also been attracting attention as a potential drug target, as recent brain imaging analysis has confirmed a correlation between tau accumulation and clinical symptoms and disease progression. Clinical trials of anti-tau antibodies against various epitopes are currently underway (Non-Patent Document 4, Non-Patent Document 84). Furthermore, as a technique for efficiently transferring antibodies into the brain for the purpose of treating Alzheimer's disease, antibodies that can efficiently pass through the blood-brain barrier (BBB) ​​have been created by adding antibodies or peptides with affinity to membrane proteins expressed in the BBB, such as transferrin receptors, to the constant region or by imparting binding properties through amino acid mutations (Non-Patent Document 5). However, currently, there are no drugs that are effective in preventing or improving cognitive decline, and the development of effective drugs for treating Alzheimer's disease is an urgent global issue. 3. Microglia Microglia are glial cells, like astrocytes and oligodendrocytes; however, unlike these cells, they originate from precursor cells that develop in the fetal yolk sac. Microglia are macrophage-like cells in the brain and function as immune cells in the central nervous system, responsible for removing toxic proteins such as amyloid beta and aggregated tau in the brain. They have also been reported to play a neurorepair or protective role in neurological disorders. Furthermore, they have been shown to play an important role in maintaining neural networks, including synaptic pruning. On the other hand, activated microglia release inflammatory cytokines and induce brain inflammation. Recent advances in genetic analysis have revealed the existence of various microglial subtypes, and their relationship to disease is a topic of future research. Regarding the relationship between microglia and Alzheimer's pathology, immunohistochemical staining of brains from Alzheimer's disease patients has been reported to correlate degenerated microglia with tau accumulation (Non-Patent Document 6). Furthermore, a subtype of dysfunctional microglia in Alzheimer's disease has been identified using immunohistochemical techniques (single cell histology) (Non-Patent Document 7). However, it remains unclear how dysfunctional microglia modify the disease. Furthermore, while dysfunctional microglia are generally identified based on their morphology, some researchers have referred to dysfunctional microglia-like microglia as "degenerated microglia" or "senescent microglia" (Non-Patent Document 8), and the meaning of these terms is not necessarily clear. Brain imaging analysis of Alzheimer's disease patients has also been performed using ligands for TSPO (translocator protein), whose expression increases when microglia are activated, and there are reports that signals detected by TSPO-PET (Positron Emission Tomography) are high in Alzheimer's disease patients (Non-Patent Document 9) and that they correlate with tau and amyloid pathology (Non-Patent Document 10). However, research into the specificity of these TSPO-PET ligands for activated microglia is still in development (Non-Patent Document 11), and a consensus has not yet been reached. In recent years, a Genome Wide Association Study (GWAS) of Alzheimer's disease (Non-Patent Document 12) has revealed that many disease-related genes are expressed in microglia. Therefore, research and development of Alzheimer's disease therapeutics targeting microglia is underway. For example, individuals with a loss-of-function (LOF) gene mutation (R47H), which causes loss of TREM2 function, are at increased risk of developing Alzheimer's disease (Non-Patent Document 13). Currently, clinical trials are being conducted on anti-TREM2 agonist antibodies (Non-Patent Document 14) and anti-CD33 inhibitory antibodies (Non-Patent Document 15) that activate microglia, with the hope of promoting the clearance of toxic proteins such as Aβ and tau by activating microglia (NCT04592874, NCT03822208). On the other hand, an anti-Sema4D antibody (Non-Patent Document 16), which suppresses activated microglia from the viewpoint of suppressing gliosis, is also undergoing clinical trials (NCT04381468). In recent years, single-cell RNA sequencing (scRNAseq) analysis of microglia in Alzheimer's disease model mice has revealed the existence of microglial subtypes associated with Alzheimer's pathology. Examples of such microglial subtypes include DAM (Disease Associated Microglia, Non-Patent Document 17), ARM (Activated Response Microglia, Non-Patent Document 18), and MGnD (Microglial Neurodegenerative Phenotype, Non-Patent Document 19). However, because there is no method to specifically regulate disease-associated microglia such as DAM, it remains unclear how these disease-associated microglia modify Alzheimer's disease, i.e., how they function. Furthermore, it remains unclear which subtypes of microglia suppress pathology and which subtypes promote pathology. Furthermore, because mRNA expression does not directly provide information on whether cells are accumulating denatured proteins, it was unclear which subtype dysfunctional microglia could be classified into or which subtype they were contained within. 4. gpNMB Glycoprotein nonmetastatic melanoma protein B (gpNMB) (also known as osteoactivin or DC-HIL, non-patent literature 20) is a single-pass transmembrane glycoprotein with 12 glycosylation sites in humans. It is normally expressed in intracellular organelles (endoplasmic reticulum, lysosomes, Golgi apparatus, melanosomes, etc.) (non-patent literature 21). However, overexpression has been reported to result in expression on the cell membrane (non-patent literature 22). gpNMB has also been reported to be expressed in cancer cells (non-patent literature 23). It has also been reported that the kringle-like domain (KLD) is important for cell proliferation and that the intracellular ITIM motif induces signals (non-patent literature 24). Furthermore, gpNMB contains a region (hereinafter referred to as the PMEL-CAF-like domain) that is homologous to the CAF (Core Amyloid Fragment) region of the family protein PMEL (Premelanosome Protein) (Non-Patent Document 25) and a PKD (Polycystic Kidney Disease homology) domain. The PKD domain is a domain that forms a β-sandwich structure by folding a β-sheet consisting of three strands and a β-sheet consisting of four strands. It was named the PKD domain because it has a characteristic structure found in polycystin-1, the gene responsible for polycystic kidney disease (Non-Patent Document 26). gpNMB is important for the function of phagosomes and lysosomes (Non-Patent Document 27), and it has been reported that gpNMB-deficient mice exhibit impaired lysosomal function (Non-Patent Document 28). Furthermore, it has been reported that gpNMB-deficient mice develop iris abnormalities and glaucoma (Non-Patent Document 29), and that gpNMB-deficient humans develop cutaneous amyloidosis (Non-Patent Document 30). It is known that gpNMB is cleaved by membrane proteases such as ADAM10 and released as soluble gpNMB (Non-Patent Document 31), and soluble gpNMB has been reported to be involved in neuroprotection (Non-Patent Document 32), anti-inflammation (Non-Patent Document 21), and cell proliferation (Non-Patent Document 33). Furthermore, it has been reported that transgenic mice overexpressing soluble gpNMB (extracellular domain gpNMB) showed improved neuronal function (Non-Patent Document 34), and that enhancing autophagy by expressing gpNMB using a lentiviral vector improved cognitive function in Alzheimer's disease model mice (APP / PS1) (Non-Patent Document 35). On the other hand, it has been reported that administration of a mouse gpNMB-specific vaccine peptide containing a partial amino acid sequence of mouse gpNMB reduces senescent vascular endothelial cells and fibroblasts, improves insulin resistance and arteriosclerosis in a high-fat diet-fed mouse model, and extends the survival time of senescence-accelerated mice. Furthermore, it has been reported that antibody-dependent cellular cytotoxicity (ADCC) activity is important in this regard, and a partial gpNMB peptide sequence effective in eliminating senescent cells has been disclosed (Patent Document 1, Non-Patent Document 36). Similarly, it has been reported that administration of a polyclonal antibody against mouse gpNMB in a high-fat diet-fed mouse model inhibited soluble gpNMB produced by the liver, thereby improving obesity and insulin resistance (Non-Patent Document 37). Known anti-gpNMB antibodies include glembatumumab (Patent Document 2), a human anti-human gpNMB-specific antibody. Glembatumumab Vedotin, a conjugate of glembatumumab and an anticancer drug, progressed to phase 2 clinical trials as a potential cancer treatment, but development was discontinued. Another anti-gpNMB antibody that binds to gpNMB expressed on the surface of cancer cells and treats cancer with an immunotoxin has also been disclosed (Patent Document 3). Furthermore, there have been reports on the acquisition of another anti-human gpNMB-specific antibody, and its application in the diagnosis and treatment of human-derived cancer cells has been described (Non-Patent Document 38). An anti-rat gpNMB-specific antibody specific to activated rat microglia has also been reported (Non-Patent Document 39). It has also been reported that an anti-mouse DC-HIL-specific antibody transduces signals into cells (Non-Patent Document 40). Regarding gpNMB expression in Alzheimer's disease (AD), immunohistochemical staining, RNA expression analysis, and cerebrospinal fluid concentration have been reported. Regarding immunohistochemical staining, it has been reported that gpNMB-expressing microglia accumulate in ApoE-positive Aβ plaques in the brains of AD patients (Non-Patent Document 41). Regarding RNA expression, scRNA-seq analysis of AppNL-G-F mice has been used to classify microglia subtypes, and it has been reported that ARM (Activated Response Microglia) produces tissue repair genes such as gpNMB, and that TREM2 production is increased and CD33 production is decreased (Non-Patent Document 18). Furthermore, in the Alzheimer's disease model mouse 5XFAD, it has been reported that gpNMB expression is increased in MGnD, suggesting that it may play a neuroprotective role (Non-Patent Document 19). On the other hand, scRNA-seq analysis of Alzheimer's disease model mice has also been reported to show gpNMB expression in dysfunctional microglia (Non-Patent Document 42). Furthermore, snRNAseq (single-nucleus RNA sequencing) using brain samples from Alzheimer's disease patients has reported the expression of TREM2, ITGAX, gpNMB, FLT1, SPP1, and other proteins in activated microglia, which have phagocytic activity and are thought to function in removing toxic proteins (Non-Patent Document 43). The relationship between type 1 microglia and Alzheimer's disease and the possible dual function of gpNMB have also been reported (Non-Patent Document 44). However, as shown in Non-Patent Document 18 and Non-Patent Document 43, it is known that many microglial subtypes exist. Furthermore, it has been reported that gpNMB is involved in autophagy function, reduces Aβ deposition in AD model mice (APP-PS1), and improves cognitive function in the Morris water maze test (Non-patent Document 35). Regarding the relationship between soluble gpNMB concentration in cerebrospinal fluid and Alzheimer's disease, some reports have shown that concentrations are elevated in AD (Non-Patent Document 19), while others have shown no correlation (Non-Patent Document 45).Recent reports have shown that gpNMB in cerebrospinal fluid correlates with the pathology and clinical symptoms of ALS (amyotrophic lateral sclerosis), PD, AD, etc. (Non-Patent Documents 80, 81, 82). Furthermore, recent genome-wide association studies (GWAS) have reported gpNMB as a risk gene for Parkinson's disease (NPL 46), suggesting its involvement in the transmission of α-synuclein, the causative agent of Parkinson's disease (NPL 47). On the other hand, it has also been reported that gpNMB deficiency does not alter synuclein-related pathology (NPL 48). Regarding immunohistochemistry, detection of gpNMB-expressing microglia has been reported in the brains of patients with Alzheimer's disease and Nasu-Hakola disease (NPL 41). Increased expression of gpNMB has also been reported in the substantia nigra through immunohistochemistry and at the protein level in Parkinson's disease (NPL 49). 5. Alzheimer's disease model mouse Currently, various Alzheimer's disease model mice have been developed and are being used in research (Non-Patent Document 50). One representative model mouse is the 5XFAD mouse (Non-Patent Document 51). This model mouse produces Aβ oligomers, which are considered to be the most toxic type of amyloid beta, and accumulates Aβ oligomers within neurons. Furthermore, the APPosk mouse (Non-Patent Document 52) ​​is a model mouse that accumulates Aβ oligomers within neurons, similar to the 5XFAD model mouse. To date, intranasal administration of rifampicin has been reported to improve pathology, restore synapse number, and improve cognitive function (Non-Patent Document 53). However, there have been no reports of clearance of intracellularly accumulated Aβ oligomers or cells that have phagocytosed or accumulated Aβ using antibodies such as anti-Aβ antibodies. Furthermore, there have been no reports of antibodies that have shown recovery of neuronal synapse number, which serves as an indicator of neuronal function or neurotransmission. Tg2576 is a Tg mouse that overexpresses the Swedish mutation (KM670 / 671NL) of the APP (Amyloid precursor protein, isoform 695) gene. It is an AD model mouse that has been reported to develop amyloid plaques (senile plaques in the brains of Alzheimer's disease patients) at around 9 months of age (Non-patent Document 54), and is widely used in research on amyloid pathology. Tau264 is a Tg mouse that expresses human tau and does not exhibit tau pathology alone (Non-Patent Document 55). However, it has been reported that crossing with AP Posk mice induces the accumulation of phosphorylated tau (Non-Patent Document 56). Tau264 is considered to be a model mouse that exhibits pathology similar to that of human Alzheimer's disease in that it exhibits phosphorylation and accumulation of unmutated wild-type tau. 6. Neurological function assessment In vivo, neurofunctional recovery is generally evaluated by behavioral tests such as the Morris water maze test, Y maze test, and novel substance exploration test, which evaluate spatial reference function and memory. In addition, in vitro evaluation by immunohistochemical staining generally involves analysis of the number of neurons by NeuN staining, which serves as an index of neurons, and analysis of the number of synapses by synaptophysin staining, which serves as an index of synapse number. In many Alzheimer's disease model mice, evaluation is performed before neuronal cell death, so neuronal function is evaluated by analyzing the number of synapses using synaptophysin staining. Many papers have reported that there is a correlation between the amount of synaptophysin in vitro and in vivo neuronal function (Non-Patent Documents 57, 58, and 59), and it is possible to evaluate the recovery of neuronal function by quantifying synaptophysin protein using synaptophysin staining, etc. 7. Alpha-synucleinopathy In Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), a Parkinsonian syndrome, the pathological formation of α-synuclein protein aggregates in the brain and throughout the body is known to cause neuronal death. These diseases, collectively known as α-synucleinopathy, are characterized by the accumulation of aberrantly aggregated α-synuclein in the brain, leading to neuronal loss. Parkinson's disease, in particular, is characterized by various behavioral disorders and autonomic nervous system symptoms. Symptoms are caused by a lack of dopamine due to the progressive loss of nerve cells in the substantia nigra of the midbrain. In Japan, it affects approximately 100 people per 100,000 population, with no gender predilection, and it often occurs in elderly people aged 50 to 60 or older. Most cases are sporadic, with the cause unknown, and multiple factors, including aging, environmental factors, and genetic factors, are thought to be involved. Hereditary PD is also observed in rare cases. There is no cure for the disease; only drugs that improve symptoms are available. Therefore, the creation of a cure based on the condition is a globally urgent issue. According to a 2018 report in JAMA Neurology, the number of Parkinson's disease patients is increasing extremely rapidly, surpassing the increase in Alzheimer's disease. Between 1990 and 2015, the global prevalence of Parkinson's disease more than doubled, and the mortality rate more than doubled. Because Parkinson's disease increases with aging, it is predicted that the number of patients will continue to increase exponentially in the future. A 2014 meta-analysis estimated that the number of Parkinson's disease patients worldwide will more than double from 6.9 million in 2015 to 14.2 million by 2040 (Non-Patent Document 73). 8. Parkinson's disease model mouse Currently, various Parkinson's disease model mice have been developed and are being used in research (Non-Patent Document 74). One representative model mouse is the A53T mutant human α-synuclein-Tg mouse (Non-Patent Document 75). This model mouse is a transgenic mouse for A53T mutant human α-synuclein. It produces α-synuclein oligomers, which are considered to be the most toxic synuclein aggregates, and accumulates α-synuclein oligomers in the hippocampus and substantia nigra (Non-Patent Document 76). In this model mouse, α-synuclein oligomers accumulate in the hippocampus before the substantia nigra, leading to cognitive impairment first, followed by the accumulation of α-synuclein oligomers in the substantia nigra, resulting in behavioral impairment. The therapeutic effects of anti-α-synuclein antibodies have been reported in mouse models (Non-Patent Document 77), but long-term administration is required and the therapeutic effects are unclear. Several anti-α-synuclein antibody drugs have already progressed to clinical trials for Parkinson's disease, but two antibodies have already been discontinued (Non-Patent Documents 78 and 79). 9. Motor function evaluation Known methods for evaluating the motor function of model mice include the rotarod test and the inverted screen test. <Rotarod test> This test measures coordination and motor learning in rodents and is particularly used to examine neurological disorders and drug effects in laboratory animals. A mouse is placed on a rotating rod, and the mouse walks along the rod while trying to avoid falling off. The speed of the rod is gradually increased, and the time it takes for the mouse to fall is measured. <Inverted Screen Test> The inverted screen test is used to measure motor strength / coordination. Untrained mice are individually placed on a square (7.5 cm x 7.5 cm) wire mesh screen (mesh composed of 12 mm squares) mounted horizontally on a metal bar. The screen is then inverted 180 degrees so that the mouse is at the bottom of the screen, and the time it takes to fall is measured. 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[0016] :8453Nordstrom et al. Neurobiology of Disease, 2021, Vol.161, Art_105543.Xiao et al. J Transl Med 2023, Vol.21, Art_178.Chatterjee et al. Neurobiol Dis 2019, Vol.132, Art_104587.Zhu et al., J Mol Neurosci 2019, Vol.69, pp643-657.Hansson et al., EMBO Mol Med 2023, Vol.15, e16359.Doroszkiewicz et al., J Clin Med 2023, 12:4689.Kawahara et al. al., J. Neurochem., (2024), Vol.00, 1-23Panza et al., Expert Opin. Investig. Drugs, 2023, Vol. 32, pp.625-634.Barreto et al., Glia, 2024, Vol.72, No.7, pp.1319-1339 There are drugs to improve the symptoms of neurodegenerative diseases, but no cures. Meanwhile, the existence of disease-related microglia that specifically appear in neurodegenerative diseases has been revealed by scRNAseq and other methods, but it was unclear which microglia were causing the pathology to progress. Furthermore, it was unclear whether identifying and specifically eliminating the dysfunctional microglia that are causing the pathology to progress would lead to therapeutic effects such as the removal of toxic proteins in nerve cells and the recovery of neuronal function. As described in the background art, gpNMB is one of the genes expressed in dysfunctional microglia that is involved in the function of autophagosomes and lysosomes. However, it was unclear whether microglia with high gpNMB expression promote the progression of the pathology or have a protective effect, or even whether it is involved in the pathology at all. Furthermore, as mentioned above, the presence of disease-associated microglia has been reported in several mouse models of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, there was no method to specifically regulate disease-associated microglia, so it was unclear how disease-associated microglia modified the disease. Furthermore, as mentioned above, there have been reports that gpNMB expressed in disease-associated microglia has neuroprotective effects and that it is expressed in dysfunctional microglia, but to date, there have been no reports of anti-gpNMB monoclonal antibodies that can bind with high affinity under physiological conditions in vivo and that can be administered to disease model animals to evaluate their efficacy.Furthermore, there have been no reports of administering high-affinity anti-gpNMB monoclonal antibodies that can act in the brain to Alzheimer's disease model mice and analyzing their effects. gpNMB is a glycoprotein rich in glycans, and in humans, there are 12 glycosylation sites. Therefore, it is not easy to create a monoclonal antibody that can recognize gpNMB expressed in cells. As mentioned above, only clinical trials have been conducted on glenbatumumab vedotin, a conjugate of glenbatumumab and an anticancer drug, in cancer types with high gpNMB expression (e.g., melanoma and breast cancer). Because glenbatumumab is an antibody specific to human gpNMB, it was not possible to evaluate its effect on endogenous gpNMB in disease model mice or disease model rats. On the other hand, it has been reported that inhibition of liver-expressed soluble gpNMB by anti-mouse gpNMB polyclonal antibodies improves obesity and insulin resistance in a high-fat diet model mouse (Non-Patent Document 37), and removal of senescent cells by mouse gpNMB-specific vaccine peptides improves arteriosclerosis and insulin resistance in a high-fat diet model mouse and extends the survival time of an accelerated senescence model mouse (Patent Document 1, Non-Patent Document 36). On the other hand, the creation of mouse-human cross-reactive anti-gpNMB antibodies for the purpose of creating a therapeutic drug for Alzheimer's disease has been extremely difficult because gpNMB has a large number of glycosylation chains, only a low mouse-human homology of about 70%, and a complex three-dimensional structure (Non-Patent Document 57). Therefore, obtaining antibodies that recognize the in vivo three-dimensional structure has been extremely difficult, and as mentioned above, no such reports have been published to date. Furthermore, because glycosylation modifications vary depending on the cells and tissues in which they are expressed, it was anticipated that obtaining antibodies that act specifically on gpNMB expressed in microglia would be extremely difficult, and it was even thought that creating anti-gpNMB antibodies (especially humanized antibodies) that bind to gpNMB expressed on the cell membrane and have mouse-human cross-reactivity would be extremely difficult. The present invention has been made in view of the above-mentioned problems, and aims to provide a means for specifically regulating dysfunctional microglia, particularly an anti-gpNMB antibody (especially a humanized antibody), as well as a pharmaceutical based on a new mechanism of action using such a means. The present inventors have found that microglia accumulate Aβ, tau, or α-synuclein intracellularly or phagocytose these substances in Alzheimer's disease, tauopathy, and Parkinson's disease model mice. Furthermore, the present inventors have found that most of these microglia are gpNMB-positive, i.e., double-stained by immunohistochemistry using anti-gpNMB and anti-Iba1 antibodies ( Figure 24 ). Furthermore, a method for scoring the level of degeneration (dysfunction) based on ramified structure has been reported (Non-Patent Document 61), and these microglia were evaluated as degenerated because of a reduced ramified structure in their morphology. Furthermore, accumulation of lipofuscin, a substance commonly observed in senescent cells, was also observed. Based on these findings, these microglia were considered to be dysfunctional microglia unable to degrade aggregated proteins or hyperfunctional microglia abnormally phagocytosing aggregated proteins. It has also been suggested that dysfunctional microglia that accumulate or phagocytosed these aggregated proteins lose their neuroprotective properties, leading to neurodegenerative pathologies (Non-Patent Document 62, Non-Patent Document 7). Furthermore, the present inventors have discovered that most of these dysfunctional microglia are gpNMB-positive, i.e., cells that double-stain in immunohistochemical staining with anti-gpNMB and anti-Iba1 antibodies. As an example, in immunohistochemical analysis of the brains of AP Posk mice, they have discovered that gpNMB-positive cells that have accumulated Aβ are anti-gpNMB and anti-Iba1 antibody-positive cells, i.e., microglia with high gpNMB expression. As used herein, "dysfunctional microglia" refers to cells that double-stain in immunohistochemical staining with anti-gpNMB and anti-Iba1 antibodies. As mentioned above, there is not necessarily agreement among researchers on what "dysfunctional microglia" means, but in this specification, "dysfunctional microglia" refers to microglia that have at least one of the following characteristics: 1) The phagocytic function and / or toxic protein degradation function are decreased or abnormally increased. 2) They release inflammatory cytokines that contribute to the progression of pathological conditions (e.g., brain inflammation). 3) The ramified structure is reduced compared to normal microglia. Regarding 1), various aggregated proteins, such as Aβ, tau, α-synuclein, lipofuscin, L-ferritin, TDP43, SOD, and polyglutamic acid proteins, are known to be targets of phagocytosis depending on the disease, and their accumulation or phagocytosis can be confirmed by observing them in microglia (Non-Patent Documents 63 and 64). Specifically, they can be identified by staining with the microglial marker Iba1, followed by detection with antibodies against aggregated proteins (e.g., anti-Aβ antibodies or anti-tau antibodies), or by autofluorescence (lipofuscin). Regarding 2), they can be confirmed by detecting the cytokines involved (Non-Patent Documents 65 and 66). Regarding 3), they can be confirmed by immunohistochemical staining (Non-Patent Document 67) or morphological observation using electron microscopy (Non-Patent Document 68) (Non-Patent Document 69). On the other hand, the term "normal microglia" as used herein refers to microglia that do not have any of the characteristics of the dysfunctional microglia described above and that function to maintain homeostasis in the body. In light of the above circumstances, the present inventors have conducted extensive research and have succeeded in obtaining an anti-gpNMB antibody (particularly a humanized antibody) that specifically binds to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB. They have also found that such an antibody can be used in a variety of applications, such as the treatment or prevention of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, by exhibiting unexpected activities such as reducing the number of dysfunctional microglia, removing amyloid β oligomers and / or phosphorylated tau and / or synuclein oligomers, increasing the number of synapses, and / or inhibiting or reversing decline in cognitive function and motor function. Furthermore, by using any means for reducing the number of dysfunctional microglia, such as the antibody, it is possible to obtain effects such as removal of amyloid β oligomers and / or phosphorylated tau and / or synuclein oligomers, increase in the number of synapses, and / or suppression or recovery of decline in cognitive function and / or motor function, and it has been found that the unexpected effect of treating or preventing various neurodegenerative diseases may be achieved, leading to the completion of the present invention. That is, the present invention relates to the following. [Item 1] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment or derivative thereof that specifically binds to at least one site in the region spanning from the PMEL-CAF-like (PMEL Core Amyloid Fragment-like) domain to the PKD domain of human gpNMB (glycoprotein nonmetastatic melanoma protein B). [Item 2] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof, or a derivative thereof, according to Item 1, which specifically binds to a region including the amino acid residues D287 and / or H301 of human gpNMB having the amino acid sequence of SEQ ID NO: 209. [Item 3] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof, or a derivative thereof, according to Item 1 or 2, which specifically binds to a region including the amino acid residues R214 and / or R215 of human gpNMB having the amino acid sequence of SEQ ID NO: 209. [Item 4] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof, or a derivative thereof, according to Item 2 or 3, which specifically binds to one or more of the following regions of human gpNMB having the amino acid sequence of SEQ ID NO: 209: a region containing the amino acid residues K257 and / or D258, a region containing the amino acid residues H268 and / or D269, a region containing the amino acid residue K282, a region containing the amino acid residue K316, a region containing the amino acid residue K186, and a region containing the amino acid residues H216 and / or R218. [Item 5] The anti-gpNMB antibody (e.g., a humanized antibody) or a fragment or derivative thereof according to any one of Items 1 to 4, wherein the anti-gpNMB antibody also specifically binds to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of mouse gpNMB. [Item 6] The anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof or a derivative thereof according to any one of Items 1 to 5, which has one or more activities selected from the group consisting of an activity to reduce the number of dysfunctional microglia, an activity to remove amyloid β oligomers and / or phosphorylated tau and / or synuclein oligomers, an activity to increase the number of synapses, and an activity to suppress or restore decline in cognitive function and / or motor function. [Item 7] The anti-gpNMB antibody (eg, a humanized antibody) or a fragment thereof or a derivative thereof according to any one of Items 1 to 6, which is a monoclonal antibody or a fragment thereof or a derivative thereof. [Item 8] At least a heavy chain variable region, wherein the heavy chain variable region is (1) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 1 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 1; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 3, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 3 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 3; and As CDR-H3, the amino acid sequence set forth in SEQ ID NO: 5, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 5 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 75.0% or more, 83.3% or more, or 91.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 5, or (2) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 17, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 17 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 17; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 19, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 19 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 19; and As CDR-H3, the amino acid sequence of SEQ ID NO: 21, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 21 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 21, or (3) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 33, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 33 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 33; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 35, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 35 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 35; and As CDR-H3, the amino acid sequence set forth in SEQ ID NO: 37, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 37 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 37; or (4) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 49, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 49 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 49; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 51, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 51 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 51; and As CDR-H3, an amino acid sequence set forth in SEQ ID NO: 53, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 53 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 68.7% or more, 75.0% or more, 81.2% or more, 87.5% or more, or 93.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 53; or (5) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 65, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 65 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 65; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 67, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 67 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 67; and As CDR-H3, an amino acid sequence set forth in SEQ ID NO: 69, or an amino acid sequence in which one, two, three, four, or five amino acid residues in the amino acid sequence set forth in SEQ ID NO: 69 have been substituted, deleted, or inserted, or an amino acid sequence having 64.2% or more, 71.4% or more, 78.5% or more, 85.7% or more, or 92.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 69, or (6) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 81, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 81 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 81; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 83, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 83 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 83; and As CDR-H3, the amino acid sequence of SEQ ID NO: 85, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence of SEQ ID NO: 85 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 85, or (7) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 97, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 97 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 97; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 99, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 99 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 99; and As CDR-H3, the amino acid sequence set forth in SEQ ID NO: 101, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 101 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 101, or (8) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 113, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 113 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 113; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 115, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 115 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 115; and As CDR-H3, an amino acid sequence set forth in SEQ ID NO: 117, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 117 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 117; or (9) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 129, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 129 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 129; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 131, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 131 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 131; and As CDR-H3, an amino acid sequence set forth in SEQ ID NO: 133, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 133 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 133; or (10) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 145, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 145 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 145; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 147, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 147 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 147; and As CDR-H3, an amino acid sequence set forth in SEQ ID NO: 149, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 149 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 149; or (11) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 161, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 161 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 161; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 163, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 163 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 163; and As CDR-H3, the amino acid sequence of SEQ ID NO: 165, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 165 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 165; or (12) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 255, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 255 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 255; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 257, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 257 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 257; and As CDR-H3, an amino acid sequence set forth in SEQ ID NO: 259, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 259 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 259, or (13) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 283, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 283 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 283; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 285, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 285 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 285; As CDR-H3, an amino acid sequence set forth in SEQ ID NO: 287, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 287 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 287; or (14) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 311, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 311 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 311; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 313, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 313 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 313; As CDR-H3, the amino acid sequence of SEQ ID NO: 315, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 315 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 315; or (15) As the CDR grafting region-H1, the amino acid sequence set forth in SEQ ID NO: 271, or the amino acid sequence set forth in SEQ ID NO: 271 in which any one, two, three, or four amino acid residues other than tyrosine at position 27, asparagine at position 32, and tryptophan at position 33 have been substituted, deleted, or inserted; as CDR-grafting region-H2, the amino acid sequence of SEQ ID NO: 273, or an amino acid sequence in which, in the amino acid sequence of SEQ ID NO: 273, any one, two, three, four, five, or six amino acid residues have been substituted, deleted, or inserted, other than aspartic acid at position 55, phenylalanine at position 57, threonine at position 58, asparagine at position 59, tyrosine at position 60, and asparagine at position 61; As the CDR-grafting region-H3, the amino acid sequence of SEQ ID NO: 275, or the amino acid sequence of SEQ ID NO: 275 in which one, two, three, four, five, or six amino acid residues other than arginine at position 98, glycine at position 100, and glycine at position 109 have been substituted, deleted, or inserted, or (16) As the CDR grafting region-H1, the amino acid sequence set forth in SEQ ID NO: 299, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 299 have been substituted, deleted, or inserted; as CDR-grafting region-H2, the amino acid sequence of SEQ ID NO: 301, or the amino acid sequence of SEQ ID NO: 301 in which one, two, three, four, five, or six amino acid residues have been substituted, deleted, or inserted, except for aspartic acid at position 52, tryptophan at position 54, aspartic acid at position 58, and proline at position 63; As the CDR grafting region-H3, the amino acid sequence of SEQ ID NO: 303, or an amino acid sequence in which, in the amino acid sequence of SEQ ID NO: 303, any one, two, three, four, five, or six amino acid residues other than arginine at position 99, threonine at position 100, tyrosine at position 102, tyrosine at position 105, tyrosine at position 107, and methionine at position 110 have been substituted, deleted, or inserted. The anti-gpNMB antibody (e.g., humanized antibody) or a fragment or derivative thereof according to any one of claims 1 to 7, having the following structure: [Item 9] At least a heavy chain variable region, wherein the heavy chain variable region comprises: (1) an amino acid sequence set forth in SEQ ID NO: 13, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 13, or (2) an amino acid sequence set forth in SEQ ID NO: 29, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 29, or (3) an amino acid sequence set forth in SEQ ID NO: 45, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 45, or (4) an amino acid sequence set forth in SEQ ID NO: 61, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 61, or (5) an amino acid sequence set forth in SEQ ID NO: 77, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 77; or (6) An amino acid sequence set forth in SEQ ID NO: 93, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 93, or (7) The amino acid sequence set forth in SEQ ID NO: 109, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 109, or (8) The amino acid sequence set forth in SEQ ID NO: 125, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 125, or (9) An amino acid sequence set forth in SEQ ID NO: 141, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 141, or (10) An amino acid sequence set forth in SEQ ID NO: 157, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 157, or (11) The amino acid sequence set forth in SEQ ID NO: 173, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 173, or (12) The amino acid sequence set forth in SEQ ID NO: 267, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 267, or (13) The amino acid sequence set forth in SEQ ID NO: 295, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 295, or (14) The amino acid sequence set forth in SEQ ID NO: 323, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 323 Item 8. The anti-gpNMB antibody (eg, humanized antibody) or a fragment or derivative thereof according to any one of Items 1 to 7, having the following structure: [Item 10] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment or derivative thereof according to Item 8 or 9, wherein the heavy chain variable region comprises a framework sequence of any class of human immunoglobulin as a framework sequence. [Item 11] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof or a derivative thereof described in any one of Items 8 to 10, further comprising a heavy chain constant region, wherein the heavy chain constant region has the amino acid sequence of a heavy chain constant region of any class of human immunoglobulin. [Item 12] At least a light chain variable region, wherein the light chain variable region comprises: (1) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 7, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 7 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 7; CDR-L2 is an amino acid sequence set forth in SEQ ID NO: 9, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 9 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 9, and As CDR-L3, the amino acid sequence of SEQ ID NO: 11, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 11 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 11, or (2) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 23, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 23 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 23; CDR-L2 is an amino acid sequence set forth in SEQ ID NO: 25, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 25 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 25, and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 27, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 27 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 27, or (3) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 39, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 39 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 39; CDR-L2 is an amino acid sequence set forth in SEQ ID NO: 41, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 41 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 41; and As CDR-L3, an amino acid sequence set forth in SEQ ID NO: 43, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 43 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 43, or (4) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 55, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 55 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 55; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 57, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 57 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 57; and As CDR-L3, an amino acid sequence set forth in SEQ ID NO: 59, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 59 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 59, or (5) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 71, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 71 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 71; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 73, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 73 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 73; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 75, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 75 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 75, or (6) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 87, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 87 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 87; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 89, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 89 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 89; and As CDR-L3, an amino acid sequence set forth in SEQ ID NO: 91, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 91 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 91, or (7) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 103, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 103 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 103; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 105, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 105 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 105; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 107, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 107 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 107, or (8) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 119, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 119 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 119; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 121, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 121 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 121; and As CDR-L3, an amino acid sequence set forth in SEQ ID NO: 123, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 123 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 123, or (9) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 135, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 135 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 135; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 137, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 137 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 137; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 139, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 139 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 139, or (10) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 151, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 151 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 151; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 153, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 153 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 153; and As CDR-L3, an amino acid sequence set forth in SEQ ID NO: 155, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 155 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 155, or (11) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 167, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 167 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 167; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 169, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 169 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 169; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 171, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 171 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 171, or (12) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 261, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 261 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 261; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 263, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 263 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 263; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 265, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 265 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 265, or (13) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 289, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 289 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 289; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 291, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 291 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 291; and As CDR-L3, an amino acid sequence set forth in SEQ ID NO: 293, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 293 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 293, or (14) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 317, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 317 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 317; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 319, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 319 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 319; and As CDR-L3, an amino acid sequence set forth in SEQ ID NO: 321, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 321 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 321, or (15) As the CDR grafting region-L1, the amino acid sequence of SEQ ID NO: 277, or the amino acid sequence of SEQ ID NO: 277 in which any one, two, three, or four amino acid residues other than isoleucine at position 29, tyrosine at position 31, and histidine at position 33 have been substituted, deleted, or inserted; as CDR grafting region-L2, the amino acid sequence of SEQ ID NO: 279, or the amino acid sequence of SEQ ID NO: 279 in which one or two amino acid residues other than threonine at position 50 have been substituted, deleted, or inserted; As the CDR-grafting region-L3, the amino acid sequence of SEQ ID NO: 281, or the amino acid sequence of SEQ ID NO: 281 in which one, two, or three amino acid residues other than histidine at position 88, glutamine at position 89, tryptophan at position 90, serine at position 92, tyrosine at position 93, proline at position 94, and cysteine ​​at position 95 have been substituted, deleted, or inserted, or (16) As the CDR grafting region-L1, the amino acid sequence of SEQ ID NO: 305, or the amino acid sequence of SEQ ID NO: 305 in which any one, two, three, four, five, or six amino acid residues other than leucine at position 31, tyrosine at position 37, and glutamic acid at position 39 have been substituted, deleted, or inserted; as CDR grafting region-L2, the amino acid sequence of SEQ ID NO: 307, or the amino acid sequence of SEQ ID NO: 307 in which one or two amino acid residues other than the lysine at position 55 have been substituted, deleted, or inserted; As the CDR grafting region-L3, the amino acid sequence of SEQ ID NO: 309, or the amino acid sequence of SEQ ID NO: 309 in which one, two, or three amino acid residues other than phenylalanine at position 94 have been substituted, deleted, or inserted. Item 12. The anti-gpNMB antibody (eg, humanized antibody) according to any one of Items 1 to 11, or a fragment thereof, or a derivative thereof, having the following structure: [Item 13] At least a light chain variable region, wherein the light chain variable region is (1) an amino acid sequence set forth in SEQ ID NO: 15, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 15, or (2) an amino acid sequence set forth in SEQ ID NO: 31, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 31, or (3) an amino acid sequence set forth in SEQ ID NO: 47, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 47, or (4) an amino acid sequence set forth in SEQ ID NO: 63, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 63, or (5) an amino acid sequence set forth in SEQ ID NO: 79, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 79, or (6) An amino acid sequence set forth in SEQ ID NO: 95, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 95, or (7) The amino acid sequence set forth in SEQ ID NO: 111, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 111, or (8) An amino acid sequence set forth in SEQ ID NO: 127, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 127, or (9) An amino acid sequence set forth in SEQ ID NO: 143, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 143, or (10) An amino acid sequence set forth in SEQ ID NO: 159, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 159, or (11) The amino acid sequence set forth in SEQ ID NO: 175, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 175, or (12) The amino acid sequence set forth in SEQ ID NO: 269, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 269, or (13) The amino acid sequence set forth in SEQ ID NO: 297, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 297, or (14) The amino acid sequence set forth in SEQ ID NO: 325, or an amino acid sequence having 60% or more homology to the amino acid sequence set forth in SEQ ID NO: 325 Item 12. The anti-gpNMB antibody (eg, humanized antibody) according to any one of Items 1 to 11, or a fragment thereof, or a derivative thereof, having the following structure: [Item 14] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment or derivative thereof according to Item 12 or 13, wherein the light chain variable region comprises a framework sequence of any class of human immunoglobulin as a framework sequence. [Item 15] An anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof or derivative thereof described in any one of Items 12 to 14, further comprising a light chain constant region, wherein the light chain constant region has the amino acid sequence of a light chain constant region of any class of human immunoglobulin. [Item 16] The anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof or a derivative thereof according to any one of Items 1 to 15, which is a Fab, scFv, diabody, nanobody, VHH, bispecific antibody, or multispecific antibody, or a derivative thereof. [Item 17] An anti-gpNMB antibody (e.g., a humanized antibody), or a fragment thereof, or a derivative thereof, which competitively binds to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB with the anti-gpNMB antibody, fragment thereof, or derivative thereof described in any one of Items 1 to 16. [Item 18] A nucleic acid molecule consisting of a polynucleotide sequence encoding the anti-gpNMB antibody (eg, humanized antibody) according to any one of Items 1 to 17, or a fragment thereof, or a derivative thereof. [Item 19] A cloning vector or expression vector comprising at least one nucleic acid molecule according to Item 18. [Item 20] A recombinant cell into which the vector according to Item 19 has been introduced. [Item 21] A method for producing the anti-gpNMB antibody (e.g., a humanized antibody) or a fragment thereof or a derivative thereof described in any one of Items 1 to 17, comprising culturing the recombinant cell described in Item 20. [Item 22] A method for producing the anti-gpNMB antibody (e.g., humanized antibody) or its fragment or derivative thereof according to any one of items 1 to 17, comprising: a region comprising amino acid residues D287 and / or H301; a region comprising amino acid residues R214 and / or R215; a region comprising amino acid residues K257 and / or D258; a region comprising amino acid residues H268 and / or D269; a region containing the amino acid residue K282; a region containing the amino acid residue K316; a region containing the amino acid residue K186; and A region containing amino acid residues H216 and / or R218 and collecting an antibody or a fragment thereof or a derivative thereof produced in the body of the animal. [Item 23] A vaccine having the activity of promoting the production of an anti-gpNMB antibody (e.g., a humanized antibody) described in any one of Items 1 to 17, or a fragment thereof, or a derivative thereof, comprising a polypeptide having an amino acid sequence identical to a region including amino acid residues D287 and / or H301 of human gpNMB having the amino acid sequence of SEQ ID NO: 209, and / or a region including amino acid residues R214 and / or R215. [Item 24] A pharmaceutical composition comprising, as an active ingredient, one or more selected from the group consisting of the anti-gpNMB antibody (e.g., a humanized antibody) or fragment thereof or derivative thereof described in any one of Items 1 to 17, the nucleic acid molecule described in Item 18, the vector described in Item 19, and the recombinant cell described in Item 20. [Item 25] Reducing the number of dysfunctional microglia in a subject, removal of amyloid beta oligomers in a subject; Increase in the number of synapses in the target removal of phosphorylated tau in a subject; Removal of synuclein and / or synuclein aggregates in a subject; Suppression or recovery of cognitive decline in a subject, Suppression or recovery of the decline in motor function of the subject, and Treating or preventing a neurodegenerative disease in a subject Item 25. The pharmaceutical composition according to Item 24, for one or more uses selected from the following: [Item 26] Contains as an active ingredient a drug having the activity of reducing the number of dysfunctional microglia. removal of amyloid beta oligomers in a subject; Increase in the number of synapses in the target Removal of phosphorylated tau and / or inhibition of tau accumulation in a subject; Removal of synuclein and / or synuclein aggregates in a subject; Suppression or recovery of cognitive decline in a subject, Suppression or recovery of the decline in motor function of the subject, and Treating or preventing a neurodegenerative disease in a subject A pharmaceutical composition for one or more uses selected from the following: [Item 27] ​​The pharmaceutical composition according to Item 24 for treating or preventing a neurodegenerative disease in a subject. [Item 28] The pharmaceutical composition according to any one of Items 25 to 27, wherein the neurodegenerative disease is a disease caused by accumulation of amyloid β, tau, or synuclein. [Item 29] Neurodegenerative diseases include Alzheimer's disease, frontotemporal lobar degeneration (FTLD-Tau), frontotemporal dementia (FTD), primary age-related tauopathy (PART), chronic traumatic encephalopathy (CTE), Pick's disease, corticobasal degeneration (CBD or CBS), progressive supranuclear palsy (PSP), globuloglial tauopathy (GGT), argyrophilic grain dementia (AGD) (argyrophilic grain disease), age-related tauastrogliotauopathy (ARTAG), familial British dementia (FBD), familial Danish dementia (FDD), FTDP17, multisystem dementia with dementia. Item 28. The pharmaceutical composition according to any one of Items 25 to 27, wherein the therapeutic agent is one or more diseases selected from tauopathy (MSTD), neurofibrillary tangle dementia, diffuse neurofibrillary tangle disease with calcification (DNTC), white matter tauopathy with globular glial inclusions (WMT-GGI), Parkinson's disease, Huntington's disease, spinocerebellar degeneration, hereditary spinocerebellar ataxia, spinal-bulbar muscular atrophy, dementia with Lewy bodies, Creutzfeldt-Jakob disease (CJD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD-TDP, FTLD-FUS), and repeat diseases. [Item 30] The pharmaceutical composition according to Item 29, wherein the neurodegenerative disease is Alzheimer's disease. [Item 31] The pharmaceutical composition according to Item 29, wherein the neurodegenerative disease is Parkinson's disease, dementia with Lewy bodies, multiple system atrophy (MSA), or amyotrophic lateral sclerosis (ALS). [Item 32] The pharmaceutical composition according to Item 30 or 31, further comprising a second active ingredient. [Item 33] The pharmaceutical composition according to Item 32, wherein the second active ingredient is one or more antibodies selected from an anti-Tau antibody, an anti-amyloid beta antibody, an anti-CD33 antibody, an anti-semaphorin 4D antibody, an anti-TNFα antibody, an anti-Sortilin antibody, an anti-galactose-specific lectin (galectin) 3 antibody, an anti-TREM2 (Triggering receptor expressed on myeloid cells 2) antibody, an anti-IL-1β antibody, an anti-CD38 antibody, an anti-MS4A antibody, and an anti-synuclein antibody. [Item 34] The pharmaceutical composition according to Item 32, wherein the second active ingredient is a vaccine comprising a full-length or partial-length polypeptide of one or more proteins selected from Tau, amyloid beta, CD33, semaphorin 4D, TNFα, sortilin, galactose-specific lectin (galectin) 3, and TREM2 (Triggering receptor expressed on myeloid cells 2), or a nucleic acid encoding the same. In the present invention, the term "medicine" is construed to encompass both the concepts of "therapeutic agent" and "prophylactic agent" unless there is a contradiction in the context. The anti-gpNMB antibodies (especially humanized antibodies) of the present invention specifically bind to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB, thereby exhibiting highly unexpected activities, such as reducing the number of dysfunctional microglia in a subject, removing amyloid-β oligomers and / or phosphorylated tau and / or synuclein oligomers, increasing the number of synapses, and / or inhibiting or reversing decline in cognitive and motor function. Furthermore, this provides pharmaceuticals based on a novel mechanism of action for the treatment or prevention of neurodegenerative diseases such as various types of Alzheimer's disease and Parkinson's disease. Figure 1 shows an alignment of the amino acid sequences of human gpNMB (isotype a) and mouse gpNMB. In the figure, the region from amino acid residues 256 to 319 is shown surrounded by a dotted line as an example of a PKD domain. The region from amino acid residues 172 to 246 is shown surrounded by a solid line as an example of a PMEL-CAF-like domain. Figure 2 shows immunostaining photographs showing the effect of administration of anti-gpNMB antibodies (GPN05-1 and GPN06-1) on reducing gpNMB-positive microglia in Alzheimer's disease model mice (APPosk mice). (A) Control, (B) GPN05-1-administered group, (C) GPN06-1-administered group. L: left brain, R: right brain, DG: dentate gyrus, CA: corneal ammonis sectors, CA3: hippocampal CA3 region, CA23: hippocampal CA2-CA3 region, Ent: entorhinal cortex, PPtA: cerebral cortical somatosensory area. Figure 3 is a graph showing the results of statistical analysis of the immunostained photographs in Figure 2. Figure 4 is an immunostained photograph showing the effect of administration of anti-gpNMB antibodies (GPN05-1 and GPN06-1) on Aβ oligomer removal in Alzheimer's disease model mice (APPosk mice). (A) Control, (B) GPN05-1 administration group, (C) GPN06-1 administration group. Figure 5 shows stained photographs showing the synaptic recovery effect of administration of anti-gpNMB antibodies (GPN05-1 and GPN06-1) in Alzheimer's disease model mice (APPosk mice). (A) Control 1 (Non-Tg mice), (B) Control 2 (APPosk mice), (C) GPN05-1 administration group, (D) GPN06-1 administration group. Figure 6 shows immunostained photographs of brain sections after antibody administration to Alzheimer's disease model mice (APPosk mice). (A) Control antibody 11E10, (B) GPN09-1 administration group, (C) GPN11-10 administration group, (D) GPN15-2 administration group, (E) GPN15-3 administration group, (F) GPN18-2 administration group. Figure 7 is a graph showing the results of statistical analysis of the immunostained photographs in Figure 6. FIG. 8 is a set of stained photographs showing the synapse recovery effect of administration of anti-gpNMB antibody (GPN18-2) in Alzheimer's disease model mice (APPosk mice).(A) Control (Non-Tg mice), (B) GPN18-2 administration group. Figure 9 shows immunostained photographs of brain sections of Alzheimer's disease model mice (APPosk mice) after antibody administration. (A) Non-administration control group, (B) GPN18-1 administration group, (C) GPN18-6 administration group, (D) GPN18-7 administration group. Figure 10 shows graphs illustrating the results of statistical analysis of the immunostained photographs of Figure 9. Figure 11 shows immunostained photographs of brain sections of Alzheimer's disease model mice (APPosk mice) after antibody administration. (A) Control antibody administration group, (B) GPN18-2 administration group, (C) GPN06-1 administration group, (D) GPN18-5 administration group, (E) 1-5E administration group. Figure 12 shows graphs illustrating the results of statistical analysis of the immunostained photographs of Figure 11. FIG. 13 is a graph showing the results of a Morris water maze test (acquisition test) in Alzheimer's disease model mice (APP / Tau-Tg mice) after administration of anti-gpNMB antibodies (GPN06-1, GPN18-2). FIG. 14 is a graph showing the results of a Morris water maze test (probe test) in Alzheimer's disease model mice (APP / Tau-Tg mice) after administration of anti-gpNMB antibodies (GPN06-1, GPN18-2). FIG. 15 is a graph showing the results of a Morris water maze test (acquisition test) in Alzheimer's disease model mice (APP / Tau-Tg mice) after administration of anti-gpNMB antibody (GPN18-2). Figure 16 is a graph showing the results of a Morris water maze test (probe test) in Alzheimer's disease model mice (APP / Tau-Tg mice) administered with an anti-gpNMB antibody (GPN18-2). Figure 17 is a photograph of double immunostained Iba1 and gpNMB brain sections from Alzheimer's disease model mice (APP / Tau-Tg mice) after antibody administration. (A1) Hippocampus of a control antibody-administered group, (A2) Hippocampus of a control antibody-administered group, (B1) Entorhinal cortex of an anti-gpNMB antibody (GPN18-2)-administered group, (B2) Entorhinal cortex of an anti-gpNMB antibody (GPN18-2)-administered group. Figure 18 is a photograph of double immunostained Aβ and phosphorylated tau brain sections from Alzheimer's disease model mice (APP / Tau-Tg mice) after antibody administration.(A1) Hippocampus of a control antibody-administered group, (A2) Entorhinal cortex of a control antibody-administered group, (B1) Hippocampus of an anti-gpNMB antibody (GPN18-2)-administered group, (B2) Entorhinal cortex of an anti-gpNMB antibody (GPN18-2)-administered group. Figure 19 shows immunostained photographs of brain sections after antibody administration to Alzheimer's disease model mice (APP / Tau-Tg mice). (A) Entorhinal cortex of a control antibody-administered group, (B) Entorhinal cortex of an anti-gpNMB antibody (GPN18-2)-administered group. Figure 20 shows the alignment of humanized mutant sequences hGPN06-1_VH1 to VH5 to mouse GPN06-1_VH. Figure 21 shows the alignment of humanized mutant sequences hGPN06-1_VL1 to VL5 to mouse GPN06-1_VL. Figure 22 shows the alignment of humanized mutant sequences hGPN18-2_VH1 to VH5 to mouse GPN18-2_VH. Figure 23 shows the alignment of humanized mutant sequences hGPN18-2_VL1 to VL5 to mouse GPN18-2_VL. Figure 24 shows photographs of fluorescent immunohistochemical staining of the hippocampus and cerebral cortex of a Parkinson's disease model mouse (A53T mutant human α-synuclein-Tg mouse). (A) is a photograph of staining with an anti-pS129 α-synuclein antibody, (B) is a photograph of double staining with an anti-gpNMB polyclonal antibody and an anti-pS129 α-synuclein antibody, and (C) is a photograph of double staining with an Iba1 antibody and an anti-gpNMB polyclonal antibody. Figure 25 is a graph showing the results of a Morris water maze test (Acquisition) in Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) administered anti-gpNMB antibodies (GPN06-1, GPN18-2). Figure 26 is a graph showing the results of a rotarod test in Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) administered anti-gpNMB antibodies (GPN06-1, GPN18-2). Figure 27 is a graph showing the results of an inverted screen test in Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) administered anti-gpNMB antibodies (GPN06-1, GPN18-2).Figure 28 shows photographs of Iba1 and gpNMB double immunostained brain sections from Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) after administration of anti-gpNMB antibodies (GPN06-1, GPN18-2). Figure 29 is a graph showing the results of statistical analysis of the immunostained photographs of Figure 28. Figure 30 is a photograph of phosphorylated α-synuclein stained brain sections from Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) after administration of anti-gpNMB antibodies (GPN06-1, GPN18-2). Figure 31 is a graph showing the results of statistical analysis of the immunostained photographs of Figure 30. Figure 32 is a photograph of α-synuclein oligomer staining of brain sections from Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) after administration of anti-gpNMB antibodies (GPN06-1, GPN18-2). Figure 33 is a graph showing the results of statistical analysis of the immunostained photographs of Figure 32. Figure 34 is a photograph of synaptophysin staining of brain sections from Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) after administration of anti-gpNMB antibodies (GPN06-1, GPN18-2). Figure 35 is a graph showing the results of statistical analysis of the immunostained photographs of Figure 34. The present invention will be described below based on specific embodiments, but the present invention is not limited to these embodiments. All documents cited in this specification, including patent publications, patent application publications, and non-patent publications, are incorporated herein by reference in their entirety for all purposes. [Anti-gpNMB antibody] One aspect of the present invention relates to an anti-gpNMB antibody (hereinafter, occasionally abbreviated as "anti-gpNMB antibody of the present invention" or "antibody of the present invention") that specifically binds to at least one region of gpNMB spanning from the PMEL-CAF-like (PMEL Core Amyloid Fragment-like) domain to the PKD domain. "At least one region of gpNMB spanning from the PMEL-CAF-like domain to the PKD domain" means, for example, at least one region spanning from amino acid residues 172 to 319 of human gpNMB having the amino acid sequence of SEQ ID NO:209. ·antibody: In the present invention, an "antibody" refers to a glycoprotein comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. The heavy chain comprises a heavy chain variable region (abbreviated as VH) and a heavy chain constant region, which comprises three domains, CH1, CH2, and CH3. The light chain comprises a light chain variable region (abbreviated as VL) and a light chain constant region. The light chain constant region comprises one domain, CL. There are two types of light chain constant regions, called λ chains and κ chains. The heavy chain constant regions include γ chains, μ chains, α chains, δ chains, and ε chains, and antibody isotypes exist, namely IgG, IgM, IgA, IgD, and IgE, depending on the heavy chain. The VH and VL regions are further subdivided into four more conserved regions (FR-1, FR-2, FR-3, FR-4) called framework regions (FRs) and three variable regions (CDR-1, CDR-2, CDR-3) called complementarity-determining regions (CDRs). The VH contains three CDRs and four FRs arranged from amino to carboxy terminus in the following order: FR-1, CDR-1 (CDR-H1), FR-2, CDR-2 (CDR-H2), FR-3, CDR-3 (CDR-H3), FR-4. The VL contains three CDRs and four FRs arranged from amino to carboxy terminus in the following order: FR-1, CDR-1 (CDR-L1), FR-2, CDR-2 (CDR-L2), FR-3, CDR-3 (CDR-L3), FR-4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The antibody of the present invention may be an antibody fragment (e.g., an antigen-binding fragment) and / or derivative, so long as it has the activity of specifically binding to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB. Examples of antibody fragments include F(ab'), Fab, and Fv. Examples of antibody derivatives include antibodies with artificially introduced amino acid mutations in the constant region, antibodies with modified constant region domain configurations, antibodies with two or more Fc domains per molecule, antibodies composed of only heavy chains or only light chains, glycosylated antibodies, bispecific antibodies, antibody conjugates bound to antibodies or antibody fragment compounds or proteins other than antibodies, antibody enzymes, nanobodies, tandem scFvs, bispecific tandem scFvs, diabodies, VHHs, and the like. In the present invention, the mere mention of "antibody" is intended to encompass antibody fragments and / or derivatives, unless otherwise specified. The antibody of the present invention may be a monoclonal or polyclonal antibody, but is preferably a monoclonal antibody. A monoclonal antibody classically refers to an antibody molecule obtained from a clone derived from a single antibody-producing cell, but it also refers to a single type of antibody molecule containing a combination of VH and VL consisting of a specific amino acid sequence. Monoclonal antibodies can also be obtained by obtaining nucleic acid molecules having gene sequences encoding the amino acids of the antibody protein, and antibodies can also be produced by genetic engineering using such nucleic acid molecules. Furthermore, techniques well known to those skilled in the art include modifying antibodies to improve their binding and specificity using genetic information such as H chains, L chains, their variable regions, and CDR sequences, and modifying antibodies from animals such as mice into human antibodies to produce antibodies with a structure suitable for use as therapeutic agents. Furthermore, human monoclonal antibodies can also be obtained by using transgenic animals into which human antibody genes have been introduced as animals to be sensitized with antigens. Alternatively, as a method that does not require sensitization of animals, a person skilled in the art can appropriately carry out a technique in which a phage library expressing the antigen-binding region of a human antibody or a portion thereof (human antibody phage display) is used to obtain antibodies that specifically bind to a corresponding antigen or phage clones consisting of a specific amino acid sequence, and then use this information to produce a human antibody (see, for example, the review in Keio J. Med., (2011), 60:37-46). Furthermore, when designing antibodies to be administered to animals other than humans, a person skilled in the art can design them using appropriate amino acid sequence information of the CDRs and variable regions, as in humanization techniques. Antibody specificity refers to the ability of an antibody to exhibit a high antigen-antibody reaction with a certain antigen. Those skilled in the art can measure antigen-antibody reactions by appropriately selecting binding assays in solid-phase or liquid-phase systems. Examples of such methods include, but are not limited to, enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA), surface plasmon resonance (SPR), fluorescence resonance energy transfer (FRET), and luminescence resonance energy transfer (LRET). Furthermore, when measuring such antigen-antibody binding, it is also possible to label the antibody and / or antigen with an enzyme, fluorescent substance, luminescent substance, radioisotope, or the like, and detect the antigen-antibody reaction using a measurement method appropriate for the physical and / or chemical properties of the labeled substance. Specific binding to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB: The antibody of the present invention specifically binds to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB. In the present invention, "gpNMB" (glycoprotein nonmetastatic melanoma protein B) (also known as osteoactivin, DC-HIL) is the aforementioned single-pass transmembrane glycoprotein. For details, see the aforementioned documents (e.g., Non-Patent Document 20). The amino acid sequence of the full-length human gpNMB (isotype a) protein is shown in SEQ ID NO: 209, and the nucleic acid sequence of the gene encoding said protein is shown in SEQ ID NO: 210. The amino acid sequence of the full-length mouse gpNMB protein is shown in SEQ ID NO: 211, and the nucleic acid sequence of the gene encoding said protein is shown in SEQ ID NO: 212. The amino acid sequence of the full-length rat gpNMB protein is shown in SEQ ID NO: 213, and the nucleic acid sequence of the gene encoding said protein is shown in SEQ ID NO: 214. An alignment of the amino acid sequences of human gpNMB (isotype a) and mouse gpNMB is shown in Figure 1. The PKD (Polycystic Kidney Disease homology) domain of gpNMB is a domain in which a three-stranded beta sheet and a four-stranded beta sheet are folded to form a beta sandwich structure. This domain was named the PKD domain because it is a characteristic structure of polycystin-1, a gene responsible for polycystinosis (Non-Patent Document 26). According to one embodiment, the region of amino acid residues 256 to 319 of human gpNMB shown in SEQ ID NO: 209 and mouse gpNMB shown in SEQ ID NO: 211 corresponds to the PKD domain. According to one embodiment, the region of amino acid residues 256 to 316 is preferred as the PKD domain, with the region of amino acid residues 257 to 316 being particularly preferred, the region of amino acid residues 268 to 316 being particularly preferred, the region of amino acid residues 270 to 316 being even more preferred, the region of amino acid residues 282 to 316 being even more preferred, and the region of amino acid residues 287 to 316 being particularly preferred. According to one embodiment, the PKD domain is preferably a region of amino acid residues 257 to 319, particularly preferably a region of amino acid residues 257 to 316, and even more preferably a region of amino acid residues 257 to 301. According to one embodiment, the PKD domain is particularly preferably a region of amino acid residues 287 to 301. In Figure 1, examples of the PKD domains of human gpNMB and mouse gpNMB are shown with the regions of amino acid residues 256 to 319 enclosed by dotted lines. As mentioned above, the PMEL-CAF-like (PMEL Core Amyloid Fragment-like) domain of gpNMB is a region homologous to the CAF region of PMEL, a protein of the same family, and in PMEL, this domain induces the formation of amyloid-like aggregates (Non-Patent Document 71). The PMEL-CAF-like domain of gpNMB is thought to prevent aggregate formation due to the presence of many N-glycosylated binding sites in the adjacent PKD domain (Non-Patent Document 70). According to one embodiment, the regions of amino acid residues 172 to 246 in human gpNMB shown in SEQ ID NO: 209 and mouse gpNMB shown in SEQ ID NO: 211 correspond to the PMEL-CAF-like domain. Of these, the region of amino acid residues 178 to 228 is preferred as the PMEL-CAF-like domain, and the region of amino acid residues 186 to 218 is even more preferred. In FIG. 1, the regions from amino acid residues 172 to 246 are shown enclosed by solid lines as examples of the PMEL-CAF-like domains of human gpNMB and mouse gpNMB. In the present invention, the "region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB" refers to a region including not only the PMEL-CAF-like domain and the PKD domain defined above, but also the region intervening between the PMEL-CAF-like domain and the PKD domain. According to one embodiment, in the case of human gpNMB shown in SEQ ID NO: 209 and mouse gpNMB shown in SEQ ID NO: 211, the region from amino acid residues 172 to 319 corresponds to the region spanning from the PMEL-CAF-like domain to the PKD domain. The antibodies of the present invention may specifically bind to at least one site in the region spanning the PMEL-CAF-like domain to the PKD domain of gpNMB of any vertebrate; however, in consideration of human pharmaceutical applications, they preferably specifically bind to at least one site in the region spanning the PMEL-CAF-like domain to the PKD domain of human gpNMB as shown in SEQ ID NO: 209. Furthermore, from the perspective of evaluating the effect on endogenous gpNMB in disease model mice or disease model rats, it is even more preferable that the antibodies of the present invention specifically bind to at least one site in the region spanning the PMEL-CAF-like domain to the PKD domain of mouse gpNMB as shown in SEQ ID NO: 211, in addition to at least one site in the region spanning the PMEL-CAF-like domain to the PKD domain of human gpNMB. In the present invention, "specifically" binding of an antibody to gpNMB means that the gpNMB binding strength is 10-fold or more, preferably 100-fold or more, and more preferably 1000-fold or more relative to the binding to proteins other than gpNMB (e.g., albumin). Furthermore, the "region spanning from the PMEL-CAF-like domain to the PKD domain" refers to the PMEL-CAF-like domain, the PKD domain, and the region between the PMEL-CAF-like domain and the PKD domain. As long as the antibody of the present invention specifically binds to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of human gpNMB, the epitope is not particularly limited. However, it is preferable that the antibodies of the present invention bind to at least one site from the PMEL-CAF-like domain to the PKD domain, and more preferably specifically bind to one or more of the following regions of human gpNMB shown in SEQ ID NO: 209: a region comprising amino acid residues K257 and / or D258 of the PKD domain, a region comprising amino acid residues H268 and / or D269 of the PKD domain, a region comprising amino acid residue K282 of the PKD domain, a region comprising amino acid residues D287 and / or H301 of the PKD domain, a region comprising amino acid residue K316 of the PKD domain, a region comprising amino acid residue K186 of the PMEL-CAF-like domain, a region comprising amino acid residues R214 and / or R215 of the PMEL-CAF-like domain, and a region comprising amino acid residues H216 and / or R218 of the PMEL-CAF-like domain. In particular, it is preferred that the antibodies of the present invention specifically bind to at least one or both of the regions containing amino acid residues D287 and / or H301 and the regions containing amino acid residues R214 and / or R215 of human gpNMB set forth in SEQ ID NO: 209. Alternatively, regardless of whether they bind to these regions, it is also preferred that the antibodies specifically bind to one or more of the regions containing amino acid residues K257 and / or D258, H268 and / or D269, K282, K316, K186, and H216 and / or R218. The epitope of human gpNMB to which the antibody of the present invention binds may be a linear epitope composed of a continuous region on the primary structure of human gpNMB (the amino acid sequence shown in SEQ ID NO: 209), as long as it includes at least one region spanning from the PMEL-CAF-like domain to the PKD domain, or a conformational epitope composed of two or more discrete partial regions on the primary structure. The region constituting the linear epitope and each partial region constituting the conformational epitope may be present in any one of the PMEL-CAF-like domain, the PKD domain, or the region between the PMEL-CAF-like domain and the PKD domain, or may span two or more regions. Furthermore, the epitope may be present only in the region spanning from the PMEL-CAF-like domain to the PKD domain, or may span other regions as well. Furthermore, as long as at least one of the multiple partial regions constituting the three-dimensional epitope is partly or entirely present within the region spanning from the PMEL-CAF-like domain to the PKD domain, the other partial regions may be present outside the region spanning from the PMEL-CAF-like domain to the PKD domain. The binding strength of the antibody of the present invention to the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB is not particularly limited, but may be determined by measuring the 50% effective concentration (EC ) of the antibody to the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB in antigen ELISA using recombinant gpNMB and / or cell ELISA using gpNMB-expressing cells. 50 ) but usually 1 x 10 -7 M or less, or 1 x 10 -8 M or less, or 1 x 10 -9 It is preferable that the antibody concentration is 50% effective (EC 50 ) refers to the antibody concentration at which the antibody shows 50% of the maximum binding affinity of the antibody to the antigen. 50 Specific measurement conditions include the conditions employed in the examples described below. The antibodies of the present invention may bind to one or more sites within other regions of gpNMB in addition to the region spanning from the PMEL-CAF-like domain to the PKD domain. Examples of amino acid sites to which the antibodies of the present invention may bind other than the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB include, but are not limited to, E385 of human gpNMB shown in SEQ ID NO: 209. ・Antibody activity: In one aspect, the antibody of the present invention preferably has various activities described below. The antibody of the present invention preferably has the activity of binding to microglia. In particular, it has been reported that gpNMB is expressed in dysfunctional microglia that have become dysfunctional in their ability to degrade toxic and unnecessary proteins due to stress (Non-Patent Document 42), and the antibody of the present invention preferably has the activity of binding to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB expressed on the cell membrane of such dysfunctional microglia. Furthermore, the antibody of the present invention preferably has various activities against microglia. Specifically, the antibody of the present invention preferably has at least one or more of the following activities: (a) Activity in reducing or eliminating dysfunctional microglia. (b) Activity of normal microglia promoting the phagocytosis of dysfunctional microglia, or activity of normalizing the dysfunction of dysfunctional microglia. (c) Activity that enhances the function of normal microglia surrounding dysfunctional microglia. The relationship between the antibodies of the present invention (a) the activity of reducing or eliminating dysfunctional microglia, (b) the activity of promoting the phagocytosis of dysfunctional microglia by normal microglia or the activity of normalizing the dysfunction of dysfunctional microglia, and (c) the activity of enhancing the action of normal microglia around dysfunctional microglia is unclear. However, without being bound by theory, it is speculated as follows: That is, it is speculated that anti-gpNMB antibodies bind to dysfunctional microglia, and normal microglia recognize them and phagocytose and remove the dysfunctional microglia, and normal microglia proliferate in the removed space, thereby promoting the normalization of the intracerebral environment, inducing the removal of toxic proteins from neurons and the restoration of synapse number. Alternatively, it is speculated that anti-gpNMB antibodies promote the phagocytic activation or proliferation of microglia, enhancing the phagocytosis of dysfunctional microglia, improving the intracerebral environment, and inducing the removal of toxic proteins from neurons and the restoration of synapse number. Furthermore, the antibody of the present invention preferably has an activity of improving or restoring the brain environment or neuronal function. Specifically, the antibody of the present invention preferably has one or more of the following activities: (x) Activity in removing amyloid β oligomers. (y) Activity that increases synapse number. (p) Activity of removing phosphorylated tau and / or suppressing tau accumulation. (q) Activity of inhibiting the formation of NFTs (neurofibrillary tangles). (r) Effect of removing amyloid beta. (s) The effect of removing synuclein and / or synuclein aggregates. Furthermore, the antibody of the present invention preferably has (z) activity to treat or prevent a neurodegenerative disease. In particular, the antibody of the present invention preferably has activity to treat or prevent a central neurodegenerative disease. Specifically, the antibody of the present invention preferably has activity to treat or prevent the neurodegenerative diseases listed below. According to one aspect of the present invention, a disease classified as a neurodegenerative disease is a disease caused by the accumulation of one or more proteins selected from amyloid beta, tau, synuclein, polyglutamine, RNA translation-derived protein, and prion. According to one aspect of the present invention, diseases classified as neurodegenerative diseases are divided into tauopathies and other neurodegenerative diseases. Specific examples of each are as follows: Specific examples of tauopathies (diseases in which tau accumulates and causes neurodegeneration) include Alzheimer's disease, frontotemporal lobar degeneration (FTLD-Tau), frontotemporal dementia (FTD), primary age-related tauopathy (PART), chronic traumatic encephalopathy (CTE), Pick's disease, corticobasal degeneration (CBD or CBS), progressive supranuclear palsy (PSP), glioglobular tauopathy (GGT), and argyrophilic grain dementia. These include argyrophilic granulomatosis (AGD), age-related tauastrogliotauopathy (ARTAG), familial British dementia (FBD), familial Danish dementia (FDD), FTDP17, multisystem tauopathy with dementia (MSTD), neurofibrillary tangle dementia, diffuse neurofibrillary tangle disease with calcification (DNTC), and white matter tauopathy with globular glial inclusions (WMT-GGI). Specific examples of neurodegenerative diseases other than tauopathies include Parkinson's disease (accumulation of α-synuclein, etc.), Huntington's disease (accumulation of mutant huntingtin, etc.), spinocerebellar degeneration (accumulation of polyglutamic acid proteins, etc.), hereditary spinocerebellar ataxia (accumulation of polyglutamic acid proteins, etc.), spinal-bulbar muscular atrophy (accumulation of polyglutamic acid proteins, etc.), dementia with Lewy bodies (accumulation of α-synuclein, etc.), multiple system atrophy (MSA, accumulation of α-synuclein, etc.), Creutzfeldt-Jakob disease (CJD) (accumulation of abnormal prion proteins, etc.), amyotrophic lateral sclerosis (ALS) (accumulation of SOD, TDP43, C9orf72, α-synuclein, γ-synuclein, etc.), frontotemporal lobar degeneration (FTLD-TDP, FTLD-FUS: accumulation of TDP43 and FUS), and repeat ataxia. In particular, with regard to amyotrophic lateral sclerosis (ALS), it has been reported that the expression of gpNMB in microglia in the spinal cord increases as the disease progresses in model mice (Non-Patent Document 85: Barreto et al., Glia, 2024, Vol. 72, No. 7, pp. 1319-1339), and therefore, similar therapeutic effects as those for Alzheimer's disease and Parkinson's disease are expected. According to the examples described below, an antibody according to one embodiment of the present invention was administered to aged Alzheimer's disease (AD) model mice, and the effects of the antibody were analyzed by evaluating brain sections by immunohistochemical staining. The results demonstrated that administration of the antibody reduced gpNMB-positive microglia in the brains of AD model mice. Even more surprisingly, it was revealed that Aβ oligomers, which are considered to be the most toxic of amyloid β, were removed from neurons in the brains of AD model mice. Even more surprising was the confirmation that administration of the antibody of the present invention restored the number of synapses in neurons in the brains of AD model mice to normal levels. Even more surprising was the demonstration of cognitive function recovery in a Morris water maze test using a newly constructed AD model mouse (APP / Tau-Tg mouse) constructed by the inventors. Furthermore, the effects of the antibody were analyzed by administering an antibody according to one embodiment of the present invention to AD model mice (APP / Tau-Tg mouse) and evaluating the effects by pathological analysis. The results showed that administration of this antibody eliminated phosphorylated tau and amyloid beta from neurons, and more surprisingly, inhibited the formation of neurofibrillary tangles (NFTs). Furthermore, according to the Examples described below, an antibody according to one embodiment of the present invention was administered to a Parkinson's disease (PD) model mouse (A53T mutant human α-synuclein-Tg mouse) and tested for cognitive and motor function to analyze the effects of the antibody. Cognitive function was evaluated using a Morris water maze test. Surprisingly, the results showed that administering the antibody of the present invention once a week for a total of just five times restored cognitive function in the Morris water maze test. Furthermore, motor function was evaluated using a rotarod test and an inverted screen test. Even more surprisingly, the results showed that administering the antibody of the present invention once a week for a total of just five times was effective in suppressing motor dysfunction. Furthermore, the effects of the antibody according to one embodiment of the present invention were analyzed by pathological analysis of the brains of Parkinson's disease (PD) model mice (A53T mutant human α-synuclein-Tg mice) administered with the antibody. The results demonstrated that administration of the antibody reduced gpNMB-positive microglia in the brains of PD model mice. Even more surprisingly, it was revealed that α-synuclein oligomers, which are considered to be the most toxic of all forms of α-synuclein (α-Syn), were removed from neurons in the brains of PD model mice. Furthermore, it was confirmed that administration of the antibody of the present invention restored the number of synapses in neurons in the brains of PD model mice to normal levels. As described above, in multiple neurodegenerative disease model mice, microglia with accumulated toxic proteins appeared as the disease progressed, and gpNMB expression was elevated in these microglia, demonstrating that administration of the antibody of the present invention inhibited or reversed the progression of neurodegenerative disease pathology and symptoms. Based on these findings, it is highly anticipated that the antibody of the present invention, which can remove microglia involved in the disease, will be effective in treating various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and ALS, by removing microglia that have accumulated toxic substances and become dysfunctional. The various activities of the antibodies of the present invention may be exhibited in vivo, ex vivo, or both in vivo and ex vivo. While any subject may exhibit these activities in vivo or ex vivo, they are preferably exhibited at least in vertebrates, more preferably in mammals, and particularly preferably in humans or non-human animals. - Amino acid and nucleic acid sequences of each antibody chain and region: The amino acid sequence of the antibody of the present invention is not particularly limited, so long as it has specific binding activity to at least one site in the region spanning the PMEL-CAF-like domain to the PKD domain of gpNMB. However, it is preferable that the antibody of the present invention has a specific amino acid sequence as each CDR sequence. Specifically, this is as follows. As used herein, "identity" of an amino acid sequence refers to the percentage of identical amino acid residues, and "similarity" refers to the percentage of identical or similar amino acid residues. The homology and identity of amino acid sequences can be determined, for example, by the BLAST method (NCBI PBLAST default conditions). Furthermore, for example, the expression "80% or more homology" clearly includes the case of "80% or more identity." Here, "similar amino acid residues" refers to amino acid residues having side chains with similar chemical properties (e.g., charge or hydrophobicity). Examples of similar amino acid residues include the following combinations: (1) Amino acid residues having aliphatic side chains: glycine (Gly or G), alanine (Ala or A), valine (Val or V), leucine (Leu or L), and isoleucine (Ile or I) residues. (2) Amino acid residues having aliphatic hydroxyl side chains: serine (Ser or S) and threonine (Thr or T) residues. (3) Amino acid residues with amide-containing side chains: asparagine (Asn or N) and glutamine (Gln or Q) residues. (4) Amino acid residues having aromatic side chains: phenylalanine (Phe or F), tyrosine (Tyr or Y), and tryptophan (Trp or W) residues. (5) Amino acid residues with basic side chains: lysine (Lys or K), arginine (Arg or R), and histidine (His or H) residues. (6) Amino acid residues with acidic side chains: aspartic acid (Asp or D) and glutamic acid (Glu or E) residues. (7) Amino acid groups with sulfur-containing side chains: cysteine ​​(Cys or C) and methionine (Met or M) residues. Furthermore, the combination of (1) and a methionine (Met or M) residue, and the combination of (4) and a histidine (His or H) residue are also considered to be similar amino acid residues. Furthermore, if a corresponding variant exists based on the germline sequence, substitution may be possible regardless of similarity. Variations based on the germline sequence include substitutions, deletions, and additions. Substitutions may also be possible with amino acids that are predicted to affect the orientation of the side chain, such as proline (Pro or P) and glycine (Gly or G). One embodiment of the antibody of the present invention includes an antibody comprising a heavy chain variable region having the CDR-H1 to H3 sequences of (1) to (14) below. As used herein, the term "CDR-grafted region" refers to a region of an antibody's amino acid sequence that has an amino acid sequence identical to or overlapping with the amino acid sequence of a CDR defined herein, and that, like a CDR, contacts an antigen to determine antigen specificity and is important for binding to the antigen. (1) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 1 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 1; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 3, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 3 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 3; and As CDR-H3, the amino acid sequence of SEQ ID NO: 5, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence of SEQ ID NO: 5 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 75.0% or more, 83.3% or more, or 91.6% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 5. (2) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 17, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 17 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 17; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 19, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 19 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 19; and As CDR-H3, the amino acid sequence of SEQ ID NO: 21, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 21 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 21. (3) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 33, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 33 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 33; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 35, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 35 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 35; and As CDR-H3, the amino acid sequence set forth in SEQ ID NO: 37, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 37 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 37. (4) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 49, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 49 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 49; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 51, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 51 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 51; and As CDR-H3, the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 53 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 68.7% or more, 75.0% or more, 81.2% or more, 87.5% or more, or 93.7% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 53. (5) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 65, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 65 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 65; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 67, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 67 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 67; and As CDR-H3, the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence in which any one, two, three, four, or five amino acid residues in the amino acid sequence of SEQ ID NO: 69 have been substituted, deleted, or inserted, or an amino acid sequence having 64.2% or more, 71.4% or more, 78.5% or more, 85.7% or more, or 92.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 69. (6) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 81, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 81 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 81; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 83, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 83 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 83; and As CDR-H3, the amino acid sequence of SEQ ID NO: 85, or an amino acid sequence in which any one, two, three, or four amino acid residues in the amino acid sequence of SEQ ID NO: 85 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 85. (7) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 97, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 97 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 97; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 99, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 99 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 99; and As CDR-H3, the amino acid sequence of SEQ ID NO: 101, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence of SEQ ID NO: 101 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 101. (8) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 113, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 113 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 113; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 115, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 115 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 115; and As CDR-H3, the amino acid sequence of SEQ ID NO: 117, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 117 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 117. (9) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 129, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 129 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 129; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 131, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 131 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 131; and As CDR-H3, the amino acid sequence of SEQ ID NO: 133, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 133 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 133. (10) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 145, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 145 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 145; As CDR-H2, an amino acid sequence set forth in SEQ ID NO: 147, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 147 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 147; and As CDR-H3, the amino acid sequence set forth in SEQ ID NO: 149, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 149 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 149. (11) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 161, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 161 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 161; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 163, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 163 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 163; and As CDR-H3, the amino acid sequence set forth in SEQ ID NO: 165, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 165 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 165. (12) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 255, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 255 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 255; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 257, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 257 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 257; and As CDR-H3, the amino acid sequence set forth in SEQ ID NO:259, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO:259 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO:259. (13) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 283, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 283 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 283; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 285, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 285 have been substituted, deleted, or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 285; As CDR-H3, the amino acid sequence set forth in SEQ ID NO:287, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO:287 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO:287. (14) As CDR-H1, an amino acid sequence set forth in SEQ ID NO: 311, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 311 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 311; as CDR-H2, an amino acid sequence set forth in SEQ ID NO: 313, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 313 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 313; As CDR-H3, the amino acid sequence of SEQ ID NO: 315, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence of SEQ ID NO: 315 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 315. As shown in Example 17 below, the present inventors investigated the importance of each amino acid residue in each CDR-grafting region sequence of the humanized anti-gpNMB antibody H1L1 (clone hGPN06-1_H1L1) in maintaining its binding activity by alanine scanning. As a result, the following residues were identified as important for maintaining binding: tyrosine at position 27, asparagine at position 32, and tryptophan at position 33 in CDR-grafting region-H1 (SEQ ID NO: 271) of the heavy chain variable region (SEQ ID NO: 295) of humanized anti-gpNMB antibody hGPN06-1_H1L1; aspartic acid at position 55, phenylalanine at position 57, threonine at position 58, asparagine at position 59, tyrosine at position 60, and asparagine at position 61 in CDR-grafting region-H2 (SEQ ID NO: 273); and arginine at position 98, glycine at position 100, and glycine at position 109 in CDR-grafting region-H3 (SEQ ID NO: 275). Meanwhile, amino acid residues in the CDR-grafting region sequences other than those described above were identified as having little effect on maintaining binding. Based on these findings, one embodiment of the antibody of the present invention includes an antibody comprising a heavy chain variable region having the CDR-grafting region-H1 to H3 sequence of (15) below (note that the following amino acid positions are shown based on the amino acid sequence of the heavy chain variable region of the humanized anti-gpNMB antibody hGPN06-1_H1L1 (SEQ ID NO: 295)). (15) As the CDR grafting region-H1, the amino acid sequence set forth in SEQ ID NO: 271, or the amino acid sequence set forth in SEQ ID NO: 271 in which any one, two, three, or four amino acid residues other than tyrosine at position 27, asparagine at position 32, and tryptophan at position 33 have been substituted, deleted, or inserted; as CDR-grafting region-H2, the amino acid sequence of SEQ ID NO: 273, or an amino acid sequence in which, in the amino acid sequence of SEQ ID NO: 273, any one, two, three, four, five, or six amino acid residues have been substituted, deleted, or inserted, other than aspartic acid at position 55, phenylalanine at position 57, threonine at position 58, asparagine at position 59, tyrosine at position 60, and asparagine at position 61; The CDR-grafting region-H3 is the amino acid sequence of SEQ ID NO: 275, or an amino acid sequence in which one, two, three, four, five, or six amino acid residues other than arginine at position 98, glycine at position 100, and glycine at position 109 in the amino acid sequence of SEQ ID NO: 275 have been substituted, deleted, or inserted. Furthermore, as shown in Example 21 below, the present inventors investigated the importance of each amino acid residue in each CDR-grafting region sequence of the humanized anti-gpNMB antibody H2L3 (clone hGPN18-2_H2L3) for maintaining binding by alanine scanning. As a result, it was identified that the following residues are important for maintaining binding: aspartic acid at position 52, tryptophan at position 54, aspartic acid at position 58, and proline at position 63 in CDR-grafting region-H2 (SEQ ID NO: 301) of the heavy chain variable region of the humanized anti-gpNMB antibody H2L3; and arginine at position 99, threonine at position 100, tyrosine at position 102, tyrosine at position 105, tyrosine at position 107, and methionine at position 110 in CDR-grafting region-H3 (SEQ ID NO: 303). On the other hand, it was identified that amino acid residues in each CDR-grafting region sequence other than those described above have almost no effect on maintaining the binding. Based on these findings, one embodiment of the antibody of the present invention is an antibody comprising a light chain variable region having the CDR-grafting region-H1 to H3 sequence shown in (16) below (note that the following amino acid positions are shown based on the amino acid sequence of the heavy chain variable region of the humanized anti-gpNMB antibody H2L3 (SEQ ID NO: 323)). (16) As the CDR grafting region-H1, the amino acid sequence set forth in SEQ ID NO: 299, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 299 have been substituted, deleted, or inserted; as CDR-grafting region-H2, the amino acid sequence of SEQ ID NO: 301, or the amino acid sequence of SEQ ID NO: 301 in which one, two, three, four, five, or six amino acid residues have been substituted, deleted, or inserted, except for aspartic acid at position 52, tryptophan at position 54, aspartic acid at position 58, and proline at position 63; As the CDR-grafting region-H3, the amino acid sequence of SEQ ID NO: 303, or an amino acid sequence in which amino acid residues in the amino acid sequence of SEQ ID NO: 303 have been substituted, deleted, or inserted at any one, two, three, four, five, or six positions other than arginine at position 99, threonine at position 100, tyrosine at position 102, tyrosine at position 105, tyrosine at position 107, and methionine at position 110. One embodiment of the antibody of the present invention includes an antibody comprising a light chain variable region having the CDR-L1 to L3 sequences of (1) to (14) below. (1) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 7, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 7 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 7; CDR-L2 is an amino acid sequence set forth in SEQ ID NO: 9, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 9 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 9, and As CDR-L3, the amino acid sequence of SEQ ID NO: 11, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 11 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 11. (2) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 23, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 23 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 23; CDR-L2 is an amino acid sequence set forth in SEQ ID NO: 25, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 25 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 25, and As CDR-L3, the amino acid sequence of SEQ ID NO:27, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO:27 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO:27. (3) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 39, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 39 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 39; CDR-L2 is an amino acid sequence set forth in SEQ ID NO: 41, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 41 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 41; and As CDR-L3, the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 43 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 43. (4) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 55, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 55 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 55; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 57, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 57 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 57; and As CDR-L3, the amino acid sequence of SEQ ID NO:59, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO:59 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO:59. (5) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 71, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 71 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 71; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 73, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 73 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 73; and As CDR-L3, the amino acid sequence of SEQ ID NO: 75, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence of SEQ ID NO: 75 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 75. (6) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 87, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 87 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 87; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 89, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 89 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 89; and As CDR-L3, the amino acid sequence of SEQ ID NO: 91, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 91 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 91. (7) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 103, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 103 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more or 83.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 103; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 105, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 105 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 105; and As CDR-L3, the amino acid sequence of SEQ ID NO: 107, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 107 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 107. (8) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 119, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 119 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 119; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 121, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 121 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 121; and As CDR-L3, the amino acid sequence of SEQ ID NO: 123, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 123 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 123. (9) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 135, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 135 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 135; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 137, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 137 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 137; and As CDR-L3, the amino acid sequence of SEQ ID NO: 139, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 139 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 139. (10) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 151, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 151 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 151; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 153, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 153 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 153; and As CDR-L3, the amino acid sequence of SEQ ID NO: 155, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence of SEQ ID NO: 155 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 155. (11) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 167, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 167 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 167; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 169, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 169 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 169; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 171, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 171 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 171. (12) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 261, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 261 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 261; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 263, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 263 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 263; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO:265, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO:265 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO:265. (13) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 289, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence set forth in SEQ ID NO: 289 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 289; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 291, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 291 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 291; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO:293, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO:293 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO:293. (14) As CDR-L1, an amino acid sequence set forth in SEQ ID NO: 317, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 317 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 317; as CDR-L2, an amino acid sequence set forth in SEQ ID NO: 319, or an amino acid sequence in which any one amino acid residue in the amino acid sequence set forth in SEQ ID NO: 319 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 319; and As CDR-L3, the amino acid sequence set forth in SEQ ID NO: 321, or an amino acid sequence in which one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 321 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 321. As shown in Example 17 below, the present inventors investigated the importance of each amino acid residue in each CDR-grafting region sequence of the humanized anti-gpNMB antibody H1L1 (clone hGPN06-1_H1L1) in maintaining its binding activity by alanine scanning. As a result, it was identified that the following residues are important for maintaining binding: isoleucine at position 29, tyrosine at position 31, and histidine at position 33 in CDR grafting region-L1 (SEQ ID NO: 277); threonine at position 50 in CDR grafting region-L2 (SEQ ID NO: 279); and histidine at position 88, glutamine at position 89, tryptophan at position 90, serine at position 92, tyrosine at position 93, proline at position 94, and cysteine ​​at position 95 in CDR grafting region-L3 (SEQ ID NO: 281) in the light chain variable region of hGPN06-1_H1L1 (SEQ ID NO: 297). On the other hand, it was identified that amino acid residues in each CDR grafting region sequence other than those mentioned above have little effect on maintaining binding. Based on these findings, one embodiment of the antibody of the present invention is an antibody comprising a light chain variable region having the CDR grafting region-L1 to L3 sequence of (15) below (note that the following amino acid positions are shown based on the amino acid sequence of the light chain variable region of humanized anti-gpNMB antibody H1L1 (sequence number 297)). (15) As the CDR grafting region-L1, the amino acid sequence of SEQ ID NO: 277, or the amino acid sequence of SEQ ID NO: 277 in which any one, two, three, or four amino acid residues other than isoleucine at position 29, tyrosine at position 31, and histidine at position 33 have been substituted, deleted, or inserted; as CDR grafting region-L2, the amino acid sequence of SEQ ID NO: 279, or the amino acid sequence of SEQ ID NO: 279 in which one or two amino acid residues other than threonine at position 50 have been substituted, deleted, or inserted; As the CDR-grafting region-L3, the amino acid sequence of SEQ ID NO: 281, or an amino acid sequence in which one, two, or three amino acid residues have been substituted, deleted, or inserted in the amino acid sequence of SEQ ID NO: 281, except for the histidine at position 88, the glutamine at position 89, the tryptophan at position 90, the serine at position 92, the tyrosine at position 93, the proline at position 94, and the cysteine ​​at position 95. Furthermore, as shown in Example 21 below, the present inventors investigated the importance of each amino acid residue in each CDR-grafting region sequence of humanized anti-gpNMB antibody H2L3 (clone hGPN18-2_H2L3) for maintaining binding by alanine scanning. As a result, the following residues were identified as important for maintaining binding: leucine at position 31 and tyrosine at position 37 in CDR-grafting region-L1 (SEQ ID NO: 305) of the light chain variable region (SEQ ID NO: 325) of humanized anti-gpNMB antibody H2L3; lysine at position 55 in CDR-grafting region-L2 (SEQ ID NO: 307); and phenylalanine at position 94 in CDR-grafting region-L3 (SEQ ID NO: 309). On the other hand, amino acid residues in each CDR-grafting region sequence other than those mentioned above were identified as having little effect on maintaining binding. Based on these findings, one embodiment of the antibody of the present invention is an antibody comprising a light chain variable region having the CDR grafting region-L1 to L3 sequence of (16) below (note that the following amino acid positions are shown based on the amino acid sequence of the light chain variable region of the humanized anti-gpNMB antibody H2L3 (sequence number 325)). (16) As the CDR grafting region-L1, the amino acid sequence of SEQ ID NO: 305, or the amino acid sequence of SEQ ID NO: 305 in which any one, two, three, four, five, or six amino acid residues other than leucine at position 31, tyrosine at position 37, and glutamic acid at position 39 have been substituted, deleted, or inserted; as CDR grafting region-L2, the amino acid sequence of SEQ ID NO: 307, or the amino acid sequence of SEQ ID NO: 307 in which one or two amino acid residues other than the lysine at position 55 have been substituted, deleted, or inserted; As the CDR-grafting region-L3, the amino acid sequence of SEQ ID NO: 309, or the amino acid sequence of SEQ ID NO: 309 in which one, two, or three amino acid residues other than phenylalanine at position 94 have been substituted, deleted, or inserted. One embodiment of the antibody of the present invention is an antibody that combines a heavy chain variable region having any of the above-mentioned CDR-H1 to H3 sequences with a light chain variable region having any of the above-mentioned CDR-L1 to L3 sequences. One embodiment of the antibody of the present invention includes an antibody having any one of the following amino acid sequences (a) to (c) as the sequence of the heavy chain variable region: (a) Any one amino acid sequence selected from SEQ ID NO: 13, SEQ ID NO: 29, SEQ ID NO: 45, SEQ ID NO: 61, SEQ ID NO: 77, SEQ ID NO: 93, SEQ ID NO: 109, SEQ ID NO: 125, SEQ ID NO: 141, SEQ ID NO: 157, SEQ ID NO: 173, and SEQ ID NO: 267. (b) An amino acid sequence having at least 60% or more, or 65% or more, or 70% or more, or 75% or more, or 80% or more, or 85% or more, or 90% or more, or 95% or more, or 96% or more, or 97% or more, or 98% or more, or 99% or more homology (preferably identity) with the amino acid sequence of (a). (c) An amino acid sequence in which 1 to 12 (preferably 1 to 11, more preferably 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) amino acid residues are substituted, deleted, or added in the amino acid sequence of (a). One embodiment of the antibody of the present invention is an antibody (especially a humanized antibody) having any of the following amino acid sequences (a) to (c) as the sequence of the heavy chain variable region: (a) Any one of the amino acid sequences selected from SEQ ID NO: 295 and SEQ ID NO: 323. (b) An amino acid sequence having at least 60% or more, or 65% or more, or 70% or more, or 75% or more, or 80% or more, or 85% or more, or 90% or more, or 95% or more, or 96% or more, or 97% or more, or 98% or more, or 99% or more homology (preferably identity) with the amino acid sequence of (a). (c) An amino acid sequence in which 1 to 12 (preferably 1 to 11, more preferably 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) amino acid residues are substituted, deleted, or added in the amino acid sequence of (a). One embodiment of the antibody of the present invention includes an antibody having any of the following (a) to (c) as the sequence of the light chain variable region: (a) Any one amino acid sequence selected from SEQ ID NO: 15, SEQ ID NO: 31, SEQ ID NO: 47, SEQ ID NO: 63, SEQ ID NO: 79, SEQ ID NO: 95, SEQ ID NO: 111, SEQ ID NO: 127, SEQ ID NO: 143, SEQ ID NO: 159, SEQ ID NO: 175, and SEQ ID NO: 269. (b) An amino acid sequence having at least 60% or more, or 65% or more, or 70% or more, or 75% or more, or 80% or more, or 85% or more, or 90% or more, or 95% or more, or 96% or more, or 97% or more, or 98% or more, or 99% or more homology (preferably identity) with the amino acid sequence of (a). (c) An amino acid sequence in which 1 to 10 (preferably 1 to 9, more preferably 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) amino acid residues are substituted, deleted, or added in the amino acid sequence of (a). One embodiment of the antibody of the present invention is an antibody (especially a humanized antibody) having any of the following amino acid sequences (a) to (c) as the sequence of the light chain variable region: (a) Any one of the amino acid sequences selected from SEQ ID NO: 297 and SEQ ID NO: 325. (b) An amino acid sequence having at least 60% or more, or 65% or more, or 70% or more, or 75% or more, or 80% or more, or 85% or more, or 90% or more, or 95% or more, or 96% or more, or 97% or more, or 98% or more, or 99% or more homology (preferably identity) with the amino acid sequence of (a). (c) An amino acid sequence in which 1 to 12 (preferably 1 to 11, more preferably 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) amino acid residues are substituted, deleted, or added in the amino acid sequence of (a). One embodiment of the antibody of the present invention is an antibody that combines any one of the heavy chain variable regions described above with any one of the light chain variable regions described above. Methods for identifying the sequences of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, or CDR-L3 in an antibody include, for example, the Kabat method (NIH Publication, (1991), No. 91-3242) and the Chothia method (J. Mol. Biol., (1997), 273[4]:927-48). These methods are common technical knowledge to those skilled in the art, and an overview of them can be found, for example, on the internet homepage of Dr. Andrew C.R. Martin's Group (http: / / www.bioinf.org.uk / abs / ). The CDRs in the present invention are described as Kabat CDRs. The framework sequences of the heavy and light chain variable regions of the immunoglobulin antibody of the present invention are preferably framework sequences of each class of vertebrate immunoglobulin, particularly those of humans or non-human animals including mice and rats. Those skilled in the art can design anti-gpNMB-specific antibodies of the present invention by appropriately combining the amino acid sequences of the above-described heavy and light chain CDRs and / or chain variable regions with the amino acid sequences of the framework regions and / or constant regions of the heavy and light chains of antibodies from humans or non-human animals, including mice and rats. In particular, humanized anti-gpNMB-specific antibodies can be produced by using the amino acid sequences of the framework regions and / or constant regions of the heavy and light chains of a human antibody. The amino acid sequences of the framework regions and / or constant regions of the heavy and light chains of the humanized antibody can be selected from, for example, human IgG, IgA, IgM, IgE, and IgD classes or variants thereof. The antibodies of the present invention are preferably of the IgG class or variants thereof, more preferably of the human IgG class or variants thereof, the human IgG4 subclass or variants thereof, or the human IgG1 subclass or variants thereof. In one example, a stabilized IgG4 constant region contains a proline at position 241 in the hinge region according to the Kabat system. This position corresponds to position 228 in the hinge region according to the EU numbering system (Proc. Natl. Acad. Sci. USA, (1969), 63[1]:78-85) and the Sequence of Proteins of Immunological Interest (Washington, DC, United States Department of Health and Human Services, 2001 and NIH Publication, (1991), No. 91-3242). In human IgG4, this residue is typically serine, and substitution of serine with proline can induce stabilization. In one example, the constant region of IgG1 can incorporate the N297A mutation to minimize its ability to bind to Fc receptors and / or fix complement. ・Competitive join: One embodiment of the present invention also includes antibodies that competitively bind with the antibodies of the present invention to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB. Such competitively binding antibodies are also included within the scope of the present invention. In the present invention, "competitive binding" refers to the phenomenon in which, when multiple types of monoclonal antibodies coexist with an antigen, the binding of one antibody to the antigen is inhibited by the binding of another antibody to the antigen. In general, this can be measured by adding varying amounts (concentrations) of a monoclonal antibody to a fixed amount (concentration) of another monoclonal antibody and measuring the amount (concentration) added at which the amount of binding of the former fixed amount of monoclonal antibody to the antigen decreases. The degree of inhibition is expressed as IC 50 A monoclonal antibody that competitively binds to the antibody of the present invention is, for example, a monoclonal antibody that exhibits an IC value of 10 nM when competitive antigen-antibody binding to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB is detected. 50 Typically, the antibody has a binding activity of 1000 nM or less, preferably 100 nM or less, and more preferably 10 nM or less. When competitive binding is measured, the antibody used can be labeled with an enzyme, a fluorescent substance, a luminescent substance, a radioisotope, or the like, and the measurement can be performed by detecting the antibody using a measurement method suitable for the physical and / or chemical properties of the labeled substance. Alternatively, a biosensor such as surface plasmon resonance (SPR) or bio-layer interferometry (BLI) can also be used. [Method of producing anti-gpNMB antibody] The antibodies of the present invention can be obtained using techniques well known to those skilled in the art. The antibodies of the present invention are polyclonal or monoclonal antibodies (Nature, (1983), 305(5934): 537-40). For example, polyclonal antibodies can be obtained by intramuscularly or subcutaneously administering to a mammal the human gpNMB protein having the amino acid sequence set forth in SEQ ID NO: 209 or a gpNMB partial peptide having a partial amino acid sequence thereof (e.g., a peptide containing a PKD domain consisting of amino acid residues 256 to 319) as an antigen, or by using an antigen-expressing polynucleotide encoding the amino acid sequence of such human gpNMB protein or gpNMB partial peptide, to express the antigen in the animal's body, thereby sensitizing the animal and recovering the antibody from the serum of the animal. Furthermore, when a peptide is used as an antigen, the antigen can be used in a form bound to a carrier protein such as BSA or KLH, or to polylysine, for example. The nonhumanized monoclonal antibodies of this invention can be obtained by sensitizing a mammal by administering human gpNMB protein or a gpNMB partial peptide, or an antigen-expressing polynucleotide encoding such human gpNMB protein or a gpNMB partial peptide, as described above, and then isolating immune cells from the mammal and fusing them with myeloma cells or the like to obtain hybridomas, which are then cloned and recovered from the culture. Methods for obtaining such monoclonal antibodies (Nature, (1992), 356

[6365] :152-4) and cell fusion techniques (Nature, (1975), 256

[5517] :495-7) have already been reported and are widely used, and the efficiency of obtaining monoclonal antibodies can be further improved by administering an immunostimulatory substance (Cancer Gene Ther., (2007), 14

[0011] :904-17). Examples of monoclonal antibodies obtained by such methods include, but are not limited to, the following: An antibody (GPN05-1) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 13 and a light chain variable region having the amino acid sequence of SEQ ID NO: 15. - An antibody (GPN06-1) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 29 and a light chain variable region having the amino acid sequence of SEQ ID NO: 31. - An antibody (GPN07-1) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 45 and a light chain variable region having the amino acid sequence of SEQ ID NO: 47. An antibody (GPN11-10) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 61 and a light chain variable region having the amino acid sequence of SEQ ID NO: 63. - An antibody (GPN15-2) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 77 and a light chain variable region having the amino acid sequence of SEQ ID NO: 79. An antibody (GPN15-3) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 93 and a light chain variable region having the amino acid sequence of SEQ ID NO: 95. -An antibody (GPN18-4) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 109 and a light chain variable region having the amino acid sequence of SEQ ID NO: 111. - An antibody (GPN18-1) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 125 and a light chain variable region having the amino acid sequence of SEQ ID NO: 127. - An antibody (GPN18-2) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 141 and a light chain variable region having the amino acid sequence of SEQ ID NO: 143. - An antibody (GPN18-6) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 157 and a light chain variable region having the amino acid sequence of SEQ ID NO: 159. - An antibody (GPN18-7) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 173 and a light chain variable region having the amino acid sequence of SEQ ID NO: 175. -An antibody (GPN09-1) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 267 and a light chain variable region having the amino acid sequence of SEQ ID NO: 269. In another production method, genes encoding the heavy and / or light chains of an antibody, more specifically, nucleic acid molecules encoding the heavy and / or light chains of an immunoglobulin, are prepared from hybridomas producing the desired antibody or phage clones obtained by human antibody phage display. Such nucleic acid molecules may be introduced into various vectors or plasmids to prepare vectors or plasmids containing the nucleic acid molecules. Next, host cells are transformed with the nucleic acid molecules, vectors, or plasmids. Examples of host cells include eukaryotic cells such as mammalian cells, insect cells, yeast cells, or plant cells, or bacterial cells. The transformed host cells are then cultured under conditions appropriate for producing the anti-gpNMB-specific antibody of the present invention. If necessary, the resulting anti-gpNMB-specific antibody of the present invention may be isolated from the host cells. The various techniques used in these procedures are all well known to those skilled in the art. Here, those skilled in the art can use known techniques to produce antibody chimeric proteins, low-molecular-weight antibodies, scaffold antibodies, etc. by genetically modifying genes encoding immunoglobulin heavy and / or light chains to introduce desired traits or by using structural information on the variable regions or CDR regions of the immunoglobulin heavy and / or light chains. Furthermore, for the purpose of improving antibody performance or avoiding side effects, modifications to the structure of the antibody constant region or modifications to the sugar chain portion can also be appropriately performed using techniques well known to those skilled in the art. [Humanized antibody] According to one embodiment, the anti-gpNMB antibody of the present invention is a humanized antibody. Hereinafter, the humanized anti-gpNMB antibody of the present invention may be referred to as the "humanized anti-gpNMB antibody of the present invention" or simply as the "humanized antibody of the present invention." Furthermore, the "anti-gpNMB antibody of the present invention" naturally includes the "humanized anti-gpNMB antibody of the present invention." Humanization of the non-humanized anti-gpNMB antibody of the present invention, that is, production of the humanized anti-gpNMB antibody of the present invention, can be carried out, for example, by the following procedure. Specifically, based on the amino acid sequence of a non-humanized (e.g., mouse) anti-gpNMB antibody obtained by the various techniques described above, the CDR regions are identified using IMGT (Lefranc, M.-P., Pommie, C., Ruiz, M., Giudicelli, V., Foulquier, E., Truong, L., Thouvenin-Contet, V., and Lefranc, G. "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains", Dev. Comp. Immunol., 27, 55-77 (2003) PMID: 12477501 LIGM:268.) and Kabat numbering. The combined IMGT / Kabat method is used to optimize the CDR loop structure. Next, a human antibody framework is selected using the CDR grafting method to maintain the CDR loop structure, thereby obtaining an antibody variant. A humanized antibody can be obtained by selecting from the obtained antibody variants those having the desired binding affinity (e.g., binding affinity to at least one site in the region extending from the PMEL-CAF-like domain to the PKD domain of gpNMB). Specifically, one human germline gene is selected that most closely resembles the amino acid sequences of the heavy and light chain variable regions of the nonhumanized (e.g., mouse) anti-gpNMB antibody obtained by the various techniques described above. Approximately 200 human IgG sequences highly homologous to the heavy and light chain variable regions are then selected as candidates using a BLAST search. Then, for example, four framework sequences are selected based on framework homology, retention of key amino acids in the framework, and loop structure. CDR grafting is then performed on these to obtain four humanized variants. Furthermore, CDR grafting is performed using a human germline sequence as the framework to obtain one humanized variant. The five obtained humanized heavy and light chain variants are combined to express and purify 25 humanized antibody variants, and their binding activity is evaluated. A humanized antibody can be obtained by comparing its activity by SPR with that of a human chimeric antibody having the mouse heavy and light chains of the parent antibody and selecting one with a predetermined binding affinity (e.g., three-fold or one-third the binding affinity). As another example, an anti-gpNMB antibody that recognizes at least one region extending from the PMEL-CAF-like domain to the PKD domain, which is recognized by the anti-gpNMB antibody disclosed herein, can be obtained directly from a human antibody-producing mouse or a human antibody phagemid library. Humanized anti-gpNMB monoclonal antibodies obtained by such methods include, but are not limited to, the following: - An antibody (hGPN06-1_H1L1) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 295 and a light chain variable region having the amino acid sequence of SEQ ID NO: 297. - An antibody (hGPN18-2_H2L3) having a heavy chain variable region having the amino acid sequence of SEQ ID NO: 323 and a light chain variable region having the amino acid sequence of SEQ ID NO: 325. [Pharmaceutical composition] The anti-gpNMB-specific antibody of the present invention is preferably used as an active ingredient of a pharmaceutical composition. That is, one aspect of the present invention relates to a pharmaceutical composition containing the anti-gpNMB-specific antibody of the present invention as an active ingredient (hereinafter, appropriately collectively referred to as the "first pharmaceutical composition of the present invention"). As described above, the anti-gpNMB-specific antibody of the present invention is expected to exhibit one or more of the following activities (a) to (c), (w) to (z), and (p) to (s) when administered to a subject such as a human. Therefore, the first pharmaceutical composition of the present invention is preferably a pharmaceutical composition used for one or more of the following activities (a) to (c), (w) to (z), and (p) to (s). (a) Use to reduce or eliminate dysfunctional microglia. (b) To promote phagocytosis of dysfunctional microglia by normal microglia, or to normalize dysfunctional microglia. (c) Use to increase the action of normal microglia around dysfunctional microglia. (w) Use for preventing or reversing decline in cognitive and / or motor function. (x) Use for removing amyloid β oligomers. (y) Use in increasing synapse number. (z) Use in treating or preventing neurodegenerative diseases. (p) Use for removing phosphorylated tau and / or suppressing tau accumulation. (q) Use in inhibiting the formation of NFTs (neurofibrillary tangles). (r) Use for removing amyloid beta. (s) Use for removing synuclein and / or synuclein aggregates. As described above, the anti-gpNMB-specific antibody of one embodiment of the present invention is presumed to have one or more of the activities (a) to (c) and, as a result, to exhibit one or more of the activities (w) to (z) and (p) to (s). Therefore, when the anti-gpNMB-specific antibody of the present invention is an antibody having one or more of the activities (a) to (c), the first pharmaceutical composition of the present invention is preferably a pharmaceutical composition used for one or more of the activities (w) to (z) and (p) to (s). Of the activities (a) to (c), it is particularly preferable that the antibody have activity (a). Furthermore, based on the results of the Examples described herein, it is highly likely that one or more of the activities (w) to (z) and (p) to (s) are exerted as a result of one or more of the activities (a) to (c), and this finding is a new finding discovered by the present inventors. Based on this finding, it is possible to prepare a pharmaceutical composition used for one or more of the activities (w) to (z) and (p) to (s) by using any drug (for example, a low molecular weight compound or a high molecular weight drug such as an antibody) having one or more of the activities (a) to (c), even if it is not the anti-gpNMB-specific antibody of the present invention. Therefore, one aspect of the present invention relates to a pharmaceutical composition (hereinafter collectively referred to as the "second pharmaceutical composition of the present invention") that contains, as an active ingredient, any drug (which may be, for example, a low molecular weight compound or a high molecular weight drug such as an antibody) having one or more of the activities (a) to (c) and is used for one or more of the activities (w) to (z) and (p) to (s). Of the activities (a) to (c), it is particularly preferred that the composition has activity (a). Hereinafter, details of the first pharmaceutical composition of the present invention and the second pharmaceutical composition of the present invention (collectively referred to as the "pharmaceutical compositions of the present invention") are, for example, as follows, but are not limited thereto. The pharmaceutical composition of the present invention may be formulated in the form of a pharmaceutical composition containing a pharmaceutically acceptable carrier and / or other additives in addition to the active ingredient (the anti-gpNMB-specific antibody of the present invention in the case of the first pharmaceutical composition of the present invention, or any drug having one or more of the activities (a) to (c) above in the case of the second pharmaceutical composition of the present invention). Formulation using a pharmaceutically acceptable carrier and / or other additives can be carried out, for example, by the method described in University of the Sciences in Philadelphia, "Remington: The Science and Practice of Pharmacy, 20th Edition," Lippincott Williams & Wilkins (2000). One form of such therapeutic or prophylactic agents is provided as a liquid preparation or lyophilized preparation prepared by dissolving, suspending, or emulsifying in a sterile aqueous or oily liquid. Examples of such solvents or dissolving solutions include aqueous solutions such as distilled water for injection and physiological saline. When an osmotic pressure regulator (e.g., D-glucose, D-sorbitol, D-mannitol, sodium chloride, etc.) is added, a suitable solubilizing agent such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), or a nonionic surfactant (e.g., polysorbate 80, polyoxyethylene hydrogenated castor oil 50) may also be used in combination. Alternatively, an oily liquid may be used as the solvent or dissolving solution. Examples of such oily liquids include sesame oil and soybean oil, and a solubilizing agent such as benzyl benzoate or benzyl alcohol may also be used in combination. In such formulations, additives such as buffers (e.g., phosphate buffers, acetate buffers), soothing agents (e.g., benzalkonium chloride, procaine hydrochloride, etc.), stabilizers (e.g., human serum albumin, polyethylene glycol, etc.), preservatives (e.g., ascorbic acid, erythorbic acid, and salts thereof, etc.), colorants (e.g., copper chlorophyll, β-carotene, Red No. 2, Blue No. 1, etc.), antiseptics (e.g., parahydroxybenzoic acid esters, phenol, benzethonium chloride, benzalkonium chloride, etc.), thickeners (e.g., hydroxypropyl cellulose, carboxymethyl cellulose, and salts thereof, etc.), stabilizers (e.g., human serum albumin, mannitol, sorbitol, etc.), and odorants (e.g., menthol, citrus flavors, etc.) may be used as appropriate. Other forms of therapeutic or prophylactic agents include solid preparations such as powders, tablets, granules, capsules, pills, suppositories, and lozenges. In the case of solid preparations administered orally, additives used include excipients (e.g., crystalline cellulose, lactose, starch, etc.), lubricants (e.g., magnesium stearate, talc, etc.), binders (e.g., hydroxypropyl cellulose, hydroxypropylmethyl cellulose, macrogol, etc.), disintegrants (e.g., starch, carboxymethyl cellulose calcium, etc.), etc. Furthermore, additives such as preservatives (e.g., benzyl alcohol, chlorobutanol, methyl parahydroxybenzoate, propyl parahydroxybenzoate, etc.), antioxidants, colorants, and sweeteners can be used as needed. Another example is a therapeutic or preventive agent for application to the mucosa, which may contain additives such as adhesives, adhesion enhancers, thickeners, and viscosifiers (e.g., mucin, agar, gelatin, pectin, carrageenan, sodium alginate, locust bean gum, xanthan gum, tragacanth gum, gum arabic, chitosan, pullulan, waxy starch, sucralfate, cellulose, and derivatives thereof) for the main purpose of imparting properties such as adsorption and retention to the mucosa. However, the form, solvent, and additives of the therapeutic or preventive agent administered to a living body are not limited to these and can be appropriately selected by one skilled in the art. The pharmaceutical composition of the present invention may contain, in addition to the active ingredient (the anti-gpNMB-specific antibody of the present invention in the case of the first pharmaceutical composition of the present invention, or any drug having one or more of the activities (a) to (c) in the case of the second pharmaceutical composition of the present invention), other existing drugs (active ingredients). Such other existing drugs (active ingredients) include, but are not limited to, various therapeutic drugs for central nervous system diseases, therapeutic drugs for neurodegenerative diseases, drugs for restoring neuronal function, and therapeutic drugs for Alzheimer's disease. Specific examples thereof include anti-tau antibodies, anti-amyloid β antibodies, anti-CD33 antibodies, anti-semaphorin 4D antibodies, anti-TNFα antibodies, anti-sortilin antibodies, anti-galactose-specific lectin (galectin) 3 antibodies, anti-TREM2 (Triggering receptor expressed on myeloid cells 2) antibodies, anti-IL-1β antibodies, anti-CD38 antibodies, anti-MS4A antibodies, and anti-synuclein antibodies. These may be used alone or in combination of two or more. The pharmaceutical composition of the present invention may also be combined with other existing drugs to form a kit. Active ingredients to be combined with the anti-gpNMB-specific antibody of the present invention include the drugs (active ingredients) described above for combination preparations. The dose of drugs other than the anti-gpNMB-specific antibody used in these combination preparations or kits can be the same as that used in conventional treatments, but this can be increased or decreased depending on the situation. The pharmaceutical composition of the present invention can be administered parenterally for the purpose of alleviating symptoms. For parenteral administration, the composition can be, for example, a nasal preparation, and liquid, suspension, solid, or other formulations can be selected. Another form of parenteral administration can be an injection, and examples of the injection include subcutaneous injection, intravenous injection, drip injection, intramuscular injection, intraventricular injection, and intraperitoneal injection. Other formulations for parenteral administration include suppositories, sublingual preparations, transdermal preparations, and transmucosal preparations other than nasal preparations. Furthermore, the composition can be administered locally intravascularly by being incorporated into or applied to a stent or intravascular embolization agent. In some cases, the composition can be administered in the form of DNA or RNA encoding the antibody, or even in the form of cells or resident bacteria that produce the antibody. The dosage of the pharmaceutical composition of the present invention varies depending on the patient's age, sex, weight, symptoms, therapeutic effect, administration method, treatment time, and the type of active ingredient contained in the pharmaceutical composition. However, typically, an adult can receive 0.1 mg to 1 g of the active ingredient per dose, preferably 0.5 mg to 300 mg, once every one to four weeks or once every one to six months. However, the dosage and frequency of administration vary depending on various conditions, and therefore, a dosage and frequency less than the above-mentioned range may be sufficient, or a dosage and frequency greater than the above-mentioned range may be required. Furthermore, the therapeutic or prophylactic agent of the present invention can achieve effects in a short administration period or can be administered over a long period by reducing side effects. [others] As described above, when administered to a subject such as a human, the anti-gpNMB-specific antibody of the present invention is expected to exhibit one or more of the following activities (a) to (c), (w) to (z), and (p) to (s): (a) Activity in reducing or eliminating dysfunctional microglia. (b) Activity that promotes the phagocytosis of dysfunctional microglia by normal microglia, or activity that normalizes dysfunctional microglia. (c) Activity that enhances the function of normal microglia surrounding dysfunctional microglia. (w) Activity to prevent or restore cognitive and / or motor function decline (x) Activity in removing amyloid β oligomers. (y) Activity that increases synapse number. (z) activity in treating or preventing neurodegenerative diseases. (p) Activity of removing phosphorylated tau and / or suppressing tau accumulation. (q) Activity of inhibiting the formation of NFTs (neurofibrillary tangles). (r) Amyloid-β removing activity. (s) activity of removing synuclein and / or synuclein aggregates; Therefore, in addition to the above-described pharmaceutical composition of the present invention, the present invention can also include the following several embodiments. That is, one aspect of the present invention relates to a method for the purpose of causing a subject to exhibit one or more of the activities (a) to (c), (w) to (z), and (p) to (s), comprising administering an effective amount of an anti-gpNMB-specific antibody of the present invention to a subject in need thereof. In particular, when the anti-gpNMB-specific antibody of the present invention is an antibody having one or more of the activities (a) to (c), the method is preferably a method for the purpose of causing a subject to exhibit one or more of the activities (w) to (z). Other details are as described above. Of the activities (a) to (c), it is particularly preferable that the antibody has at least (a). Another aspect of the present invention relates to a method for administering an effective amount of any drug (which may be, for example, a low molecular weight compound or a high molecular weight drug such as an antibody) having one or more of the activities (a) to (c) to a subject in need thereof, for the purpose of exerting one or more of the activities (w) to (z) and (p) to (s) in the subject. The details are as described above. In particular, it is preferable that the drug has at least (a) of the activities (a) to (c). Another aspect of the present invention relates to an anti-gpNMB-specific antibody of the present invention for use in exerting one or more of the activities (a) to (c), (w) to (z), and (p) to (s) in a subject. In particular, when the anti-gpNMB-specific antibody of the present invention is an antibody having one or more of the activities (a) to (c), it is preferable that the antibody be used to exert one or more of the activities (w) to (z) and (p) to (s) in a subject. Other details are as described above. It is particularly preferable that the antibody has at least a) of the activities (a) to (c). Another aspect of the present invention relates to any drug (for example, a low molecular weight compound or a high molecular weight drug such as an antibody) having one or more of the activities (a) to (c) for use in a subject to exert one or more of the activities (w) to (z) and (p) to (s). Details are as described above. In particular, it is preferable that the drug has at least (a) of the activities (a) to (c). That is, one aspect of the present invention relates to the use of an anti-gpNMB-specific antibody of the present invention in the manufacture of a pharmaceutical intended to exert one or more of the activities (a) to (c), (w) to (z), and (p) to (s) in a subject. In particular, when the anti-gpNMB-specific antibody of the present invention is an antibody having one or more of the activities (a) to (c), the pharmaceutical is preferably intended to exert one or more of the activities (w) to (z) and (p) to (s) in a subject. Other details are as described above. Of the activities (a) to (c), it is particularly preferable that the pharmaceutical has at least (a). Another aspect of the present invention relates to the use of any drug (for example, a low molecular weight compound or a high molecular weight drug such as an antibody) having one or more of the activities (a) to (c) in the manufacture of a pharmaceutical intended to exert one or more of the activities (w) to (z) and (p) to (s) in a subject. The details are as described above. In particular, it is preferable that the drug has at least (a) of the activities (a) to (c). The present invention will be described in more detail below with reference to examples. However, these examples are merely examples shown for the convenience of explanation, and the present invention is not limited to these examples in any sense. [Standard procedure] Antigen ELISA (Enzyme-Linked Immunosorbent Assay): Recombinant soluble human or mouse gpNMB was diluted with PBS to a concentration of 2 μg / mL, added to a 96-well plate (Nunc, MaxiSorp) at 50 μL / well, and allowed to stand overnight at 4° C. This 96-well plate was blocked with 3% BSA / PBS and used as the recombinant soluble gpNMB-immobilized 96-well plate for ELISA. Anti-gpNMB antibody-containing hybridoma culture supernatant or 3% BSA / PBS solution was added at 30 μL / well to the above-mentioned recombinant soluble gpNMB-immobilized 96-well plate and incubated at room temperature for 1 hour. After washing with a washing solution (TBS-T: Tris-Buffered Saline, 0.025% Tween® 20), an anti-mouse IgG antibody-ALP conjugate (SBA, 1050-04), an antibody reactive with all mouse IgG isotypes, was diluted 1:1000 with 3% BSA / PBS and added at 30 μL / well. The incubation was continued at room temperature for 1 hour. A substrate solution (PNPP (p-nitrophenyl phosphate), 1 mg / mL) was added at 100 μL / well and incubated at room temperature for 1 hour. The absorbance at 405-550 nm was calculated. The absorbance values ​​obtained were used to evaluate binding activity. ・Cell-based ELISA: gpNMB-expressing cells were seeded on a polylysine-coated 96-well plate and allowed to adhere. After removing the culture supernatant, the cells were fixed with 10% formalin at room temperature for 10 minutes. The supernatant was then removed, and the cells were blocked with 3% BSA / PBS solution and stored in a refrigerator. The blocking solution was removed from the resulting cell fixation plate, and antibody-containing medium or solution was added at 30 μL / well and incubated at room temperature for approximately 1 hour to 1 hour and 30 minutes. The plate was then washed 2 to 4 times with washing solution (TBS-T), and a 10,000-fold diluted solution of anti-mouse IgG-HRP-labeled secondary antibody was added and incubated at room temperature for 1 hour. The plate was then washed 2 to 4 times with washing solution (TBS-T), and 50 μL / well of substrate TMB solution was added and incubated at room temperature for 30 minutes. The reaction was then stopped by adding 50 μL / well of 1N sulfuric acid, and the absorbance at 450 to 650 nm was calculated. The obtained absorbance value was evaluated as binding activity. Example 1: Preparation and screening of mouse or rat monoclonal antibodies (antigen ELISA and cell ELISA): Mouse or rat monoclonal antibodies can be produced by the hybridoma method described in Koehler et al., Nature, (1975), 256:495-497, for example. Anti-gpNMB antibodies were prepared by immunizing mice or rats with nucleic acids, proteins, or peptides containing the full-length or partial amino acid sequence (SEQ ID NO: 209) or nucleic acid sequence (SEQ ID NO: 210) of human gpNMB (isotype a), or the amino acid sequence (SEQ ID NO: 211) or nucleic acid sequence (SEQ ID NO: 212) of mouse gpNMB, and collecting lymphocytes from mice or rats that showed elevated antibody titers. All animal experiments were conducted in accordance with the regulations of the institution. Hybridomas were produced by fusing lymphocytes collected from mice or rats with mouse myeloma cell lines (P3U1 (P3X63Ag8U.1) or SP2 / 0 (SP2 / 0-Ag14)) using standard hybridoma techniques. Hybridomas were selected using so-called HAT medium containing hypoxanthine, aminopterin, and thymidine. An alignment of the amino acid sequences of human gpNMB (isotype a) (SEQ ID NO: 209) and mouse gpNMB (SEQ ID NO: 211) is shown in FIG. 1. In the figure, the region from amino acid residues 256 to 319 is shown surrounded by a dotted line as an example of a PKD domain. The region from amino acid residues 172 to 246 is shown surrounded by a solid line as an example of a PMEL-CAF-like domain. Using the culture medium of the obtained hybridomas, binding assessment was performed by antigen ELISA using immobilized recombinant human soluble gpNMB (SEQ ID NO: 221) or mouse soluble gpNMB (SEQ ID NO: 223), and by cell ELISA using cells expressing a protein containing human gpNMB (SEQ ID NO: 209), and wells containing positive hybridomas were selected. The hybridomas contained in these wells were single cloned by limiting dilution. These single cloned positive hybridomas were cultured, and monoclonal antibodies were purified from the culture medium using a protein A column (Ab-Capcher, Proteinova), to obtain multiple anti-gpNMB antibodies. Example 2: Determination of antibody sequence: In order to determine the gene sequences of the light and heavy chains of each anti-gpNMB antibody clone obtained in Example 1, SMARTer （登録商標） The RACE method was performed. Gene fragments of the heavy and light chains of the antibody, including the initiation and termination codons, were extracted from RNA derived from the hybridoma producing the antibody using SMARTer. （登録商標） The DNA was obtained by RACE and its base sequence was determined. （登録商標） First-strand cDNA was synthesized using a RACE 5' / 3' Kit (634859, Clontech), and the cDNA was then amplified by PCR. Using the cDNA as a template, PCR was performed using primers specific to the universal sequence provided with the kit and primers specific to the heavy and light chains of the antibody. The resulting PCR product was used as a 5' RACE PCR product for TA cloning. Regarding the sequencing of the rat monoclonal antibody gene, PCR reactions were carried out on the variable regions of the heavy and light chains of the rat antibody, and the resulting PCR fragments were ligated to mouse constant regions to form mouse chimeric antibodies, which were then sequenced. For TA cloning, 5' RACE PCR products were electrophoresed, and cDNA fragments containing the desired molecular weight were purified using a QIAEX II Gel Extraction Kit (20021, Qiagen). The purified cDNA was incubated at 72°C for 5 minutes using TaKaRa-Taq (R001A, Takara) to add adenine to the 3' end. The cDNA fragment was cloned into the pMD20-T vector (hereinafter referred to as the MD20 vector) using a Mighty TA-cloning Kit (6028, Takara) according to the attached protocol. The MD20 vector containing the cDNA of interest was transformed into Escherichia coli TOP10 and cultured on agar medium containing 100 μg / mL ampicillin. Insertion of the desired cDNA fragment into the MD20 vector was confirmed by colony PCR. The nucleotide sequence of the cloned cDNA fragment was identified. Similarly, the nucleotide sequence of the 3' RACE PCR product was identified, and the full-length sequence of each antibody gene was determined. Of the anti-gpNMB antibody clones obtained in Example 1, for GPN05-1, GPN06-1, GPN07-1, GPN09-1, GPN11-10, GPN15-2, GPN15-3, GPN18-1, GPN18-2, GPN18-4, GPN18-5, GPN18-6, GPN18-7, and 1-5E, the amino acid sequences and SEQ ID NOs of the heavy and light chain variable regions (VH and VL, respectively) and the complementarity determining regions (CDR-H1 to H3 and CDR-L1 to L3, respectively) contained therein, determined by the above procedures, are shown in Tables 1-1 to 1-5. [Example 3] Analysis of binding activity of anti-gpNMB antibody to microglia (cell ELISA): To evaluate the binding ability of each anti-gpNMB antibody obtained in Example 1 to microglia, brain cells were collected from the brains of 1- to 2-day-old mice or rats, cultured for approximately one week, and then the adherent cells were shaken for approximately one hour to collect the detached cells, and mouse or rat microglia were collected. The collected mouse or rat microglia were suspended in 20% FBS / DMEM-GlutaMax and diluted to 2 × 10 4 The cells were seeded onto a 96-well plate at 1 / well and cultured in a CO2 incubator at 37°C for 1 to 2 days to allow adhesion, then fixed with mild formaldehyde and blocked with 3% BSA / PBS to prepare a cell ELISA plate. The blocking solution was removed from mouse or rat microglia-immobilized ELISA plates, and anti-gpNMB antibody dilution (3% BSA / PBS solution) was added at 30 μL / well and incubated at room temperature for 1 hour. After washing with washing solution, antibodies specifically reacting with mouse IgG, such as anti-mouse IgG antibody-HRP conjugate (MBL, Code No. 330) or anti-mouse IgG antibody-ALP conjugate (SBA, 1050-04), were added at 50 μL / well and incubated at room temperature for 1 hour. HRP substrate (ELISA-Star™ peroxidase chemiluminescent substrate, Fujifilm Wako Pure Chemical Industries, Ltd.) was added at 100 μL / well, and the luminescence intensity was immediately measured over 1 to 10 seconds. The resulting luminescence intensity was used to evaluate binding activity. Alternatively, 100 μL / well of ALP substrate (PNPP) was added and incubated at room temperature for 1 hour. The absorbance at 405-550 nm was measured, and the resulting absorbance value was evaluated as binding activity. As a result, the binding ability of anti-gpNMB antibody to mouse microglia and rat microglia was confirmed. [Example 4] Analysis of binding site of anti-gpNMB antibody (antigen ELISA): In order to analyze the binding site of each anti-gpNMB antibody obtained in Example 1 on human gpNMB protein, the following experiment was carried out. First, based on the amino acid sequence of the human gpNMB extracellular domain (SEQ ID NO: 215; in this amino acid sequence, amino acid residues 1 to 21 constitute a signal peptide, and amino acid residues from position 22 onward constitute an isolated peptide of the human gpNMB extracellular domain), an N-terminal deletion mutant (hgpNMB_d07_76-498) and a C-terminal deletion mutant (hgpNMB_d07_76-498) of the human gpNMB extracellular domain shown in Table 2 below were identified. hgpNMB_d03_1-251, hgpNMB_d04_1-321, hgpNMB_d05_1-375, hgpNMB_d06_1-418, hgpNMB_d13_1-412, hgpNMB_d14_1-406, hgpNMB_d15_1-400, hgpNMB_d16_1-394, hgpNMB_d17_1-388, hgpNMB_d18_1-382, and hgpNMB_d19_1-234) were constructed. The gpNMB gene was inserted into a transient animal cell expression vector, and the vector was expressed in the medium using an Expi293 Expression System (A14635, Thermo Fisher Scientific). The purified protein was then affinity-purified using Ni-NTA agarose (143-09763, FUJIFILM Wako) using a histidine tag attached to the C-terminus. Next, 17 nmol / L of purified recombinant human soluble gpNMB (SEQ ID NO: 221), the N-terminal deletion mutants (hgpNMB_d07_76-498) and C-terminal deletion mutants (hgpNMB_d03_1-251, hgpNMB_d04_1-321, hgpNMB_d05_1-375, hgpNMB_d06_1-41) of the extracellular domain of human gpNMB shown in Table 2 were added to a 96-well plate for ELISA. 8, hgpNMB_d13_1-412, hgpNMB_d14_1-406, hgpNMB_d15_1-400, hgpNMB_d16_1-394, hgpNMB_d17_1-388, hgpNMB_d18_1-382, and hgpNMB_d19_1-234), and purified recombinant mouse soluble gpNMB (SEQ ID NO: 223) were added at 100 μL / well and allowed to stand at room temperature for 90 minutes. After blocking with 3% BSA / PBS, antigen ELISA plates were prepared. The blocking solution was removed from the antigen ELISA plate, and anti-gpNMB antibody dilution (3% BSA / PBS solution) was added at 50 μL / well and allowed to react at room temperature for 1 hour. After washing with washing solution, an antibody that specifically reacts with mouse IgG, anti-mouse IgG antibody-ALP conjugate (SBA, 1050-04), was added at 50 μL / well and allowed to react at room temperature for 1 hour. Substrate (PNPP) was added at 100 μL / well and allowed to react at room temperature for 1 hour, and the absorbance at 405-550 nm was calculated. The obtained absorbance value was evaluated as binding activity. [Example 5] Determination of epitopes of anti-gpNMB antibodies (antigen ELISA): In order to determine the epitopes of each anti-gpNMB antibody obtained in Example 1 on gpNMB, the following experiment was carried out. First, we investigated the C-terminal deletion mutant (hgpNMB_d19_1-234) and point mutants (hgpNMB_d22_K245A, hgpNMB_d23_D252A, hgpNMB_d24_E253A, hgpNMB_d25_D264A, hgpNMB_d26_H272A, hgpNMB_d28_H297A, hgpNMB_d30_H376A) of the extracellular domain of human gpNMB shown in Table 3 below. , hgpNMBd31_D247A_R248A, hgpNMB_d34_D287A, hgpNMB_d35_H301A, hgpNMB_d36_R331A_K334A, hgpNMB_d37_K344A_D347A, hgpNMB_d38_D356A, hgpNMB_d39_E360A, hgpNMB_d40_E367A, and hgpNMB_d41_R373A) were constructed. The purified gpNMB protein was prepared by inserting the gpNMB gene into a transient animal cell expression vector and expressing it in the medium using an Expi293 Expression System (A14635, Thermo Fisher Scientific). The purified protein was then affinity-purified using Ni-NTA agarose (143-09763, FUJIFILM Wako) using a histidine tag attached to the C-terminus. A summary of these C-terminal deletion mutants and point mutants of the human gpNMB extracellular domain is shown in Table 3. Using these alanine point mutants of the human gpNMB extracellular domain, antigen ELISA analysis was performed using the same procedure as described in Example 4 to evaluate the binding ability of each anti-gpNMB antibody. Specifically, each of the C-terminal deletion mutants and alanine point mutants of the human gpNMB extracellular domain shown in Table 2 above was added to a 96-well ELISA plate at a concentration of 17 nmol / L at 100 μL / well and allowed to stand at room temperature for 90 minutes. Subsequently, blocking was performed with 3% BSA / PBS to prepare an antigen ELISA plate. The blocking solution was removed from the antigen ELISA plate, and anti-gpNMB antibody dilution (3% BSA / PBS solution) was added at 50 μL / well and allowed to react at room temperature for 1 hour. After washing with washing solution, an antibody that specifically reacts with mouse IgG, anti-mouse IgG antibody-ALP conjugate (SBA, 1050-04), was added at 50 μL / well and allowed to react at room temperature for 1 hour. Substrate (PNPP) was added at 100 μL / well and allowed to react at room temperature for 1 hour, and the absorbance at 405-550 nm was calculated. The resulting absorbance value was evaluated as binding activity. For absorbance at 2 nM, mutants that showed a 50% or greater decrease in absorbance compared to the mutant that showed maximum absorbance were marked with a +, and mutants that showed a 50% or greater decrease in absorbance were marked with a -. The results are shown in Table 4 below. Furthermore, binding to alanine point mutants of the N-terminal human gpNMB extracellular domain was analyzed by antigen ELISA in the same manner using an anti-gpNMB antibody bound to a C-terminal deletion mutant of the human gpNMB extracellular domain (hgpNMB_d19_1-234). First, the C-terminal deletion mutant (hgpNMB_d19_1-234) and point mutants (hgpNMB_d19_1-234, hgpNMB_d43_1-234_R77A, hgpNMB_d44_1-234_D85A, hgpNMB_d45_1-234_R104A, hgpNMB_d47_1-234_E117A,K118A, hgpNMB_d48_1-234_R121A,E123A, hgpNMB_d49_1-234_D129A, hgpNMB_d50_1-234_E140A,K118A, hgpNMB_d51_1-234_D141A,K118A, hgpNMB_d52_1-234_D142A,K118A, hgpNMB_d53_1-234_D143A,K144A, hgpNMB_d54_1-234_D145A,K146A, hgpNMB_d55_1-234_D146A,K147A, hgpNMB_d56_1-234_D147A,K148A, hgpNMB_d57_1-234_D149A,K149A, hgpNMB_d58_1-234_D150A,K151A, hgpNMB_d59_1-234_D151B, hgpNMB_d60_1-234_D160A,K161A, hgpNMB_d61_1-234_D162A 141A, hgpNMB_d51_1-234_D143A, E145A, hgpNMB_d52_1-234_H152A, H153A , hgpNMB_d53_1-234_D158A, K160A, hgpNMB_d54_1-234_H164A, H165A, hgpN The following clones were prepared: hgpNMB_d55_1-234_R169A, hgpNMB_d58_1-234_R189A, hgpNMB_d59_1-234_R193A, hgpNMB_d61_1-234_R214A, R215A, and hgpNMB_d64_1-234_D109A. The purified gpNMB protein was expressed in culture medium using an Expi293 Expression System (A14635, Thermo Fisher Scientific) after inserting the gpNMB gene into a transient animal cell expression vector. The purified protein was then affinity purified using Ni-NTA agarose (143-09763, FUJIFILM Wako) using the histidine tag attached to the C-terminus. The C-terminal deletion mutants and point mutants of the human gpNMB extracellular domain are summarized in Table 5 below. Using these human gpNMB extracellular domain alanine point mutants, antigen ELISA analysis was performed using the same procedure as described in Example 4 to evaluate the binding ability of each anti-gpNMB antibody. Specifically, the C-terminal deletion mutants and each gpNMB alanine point mutant shown in Table 5 above were added to a 96-well ELISA plate at a concentration of 17 nmol / L at 100 μL / well and allowed to stand at room temperature for 90 minutes. Subsequently, blocking was performed with 3% BSA / PBS to prepare an antigen ELISA plate. The blocking solution was removed from the antigen ELISA plate, and anti-gpNMB antibody dilution (3% BSA / PBS solution) was added at 50 μL / well and allowed to react at room temperature for 1 hour. After washing with washing solution, an antibody that specifically reacts with mouse IgG, anti-mouse IgG antibody-ALP conjugate (SBA, 1050-04), was added at 50 μL / well and allowed to react at room temperature for 1 hour. Substrate (PNPP) was added at 100 μL / well and allowed to react at room temperature for 1 hour, and the absorbance at 405-550 nm was calculated. The obtained absorbance value was evaluated as binding activity. The results are shown in Table 6 below (note that, as mentioned above, in the amino acid sequence shown in SEQ ID NO:215, amino acid residues 1 to 21 constitute the signal peptide, and amino acid residues from position 22 onwards constitute the isolated peptide of the human gpNMB extracellular domain. Accordingly, each mutant protein shown in Table 6 below also starts from the amino acid residue at position 22.) The binding activity to the above C-terminal deletion mutant (hgpNMB_d19_22-234) was defined as 100%, and a + sign was used when the binding activity was 50% or less. A - sign was used when the binding activity was 50% or more. Taking into consideration the stability of the purified gpNMB mutants and the mutation sites that affected the binding properties, the epitope of each anti-gpNMB antibody was determined. As a result, it was revealed that antibody clones GPN18-1, GPN18-2, GPN18-6, and GPN18-7 interact with amino acids (R214 and / or R215) present in the PMEL-CAF-like region. On the other hand, antibody clone GPN18-5 was found to additionally recognize the N-terminal portion. Antibody clone 1-5E is an anti-gpNMB antibody obtained by immunization with a vaccine peptide as reported in a paper (Non-Patent Document 36), and the recognized epitope is "RRGDGRWKD," amino acid residues 63-71 at the N-terminus. Example 6: Production of recombinant anti-gpNMB antibody: A gene sequence encoding the H chain and L chain of the anti-gpNMB antibody obtained in Example 2, each with a gene sequence encoding a signal sequence added to the 5' end, was inserted into the animal cell expression vector pcDNA3.4 to prepare a plasmid. The antibody was transiently expressed using an ExpiCHO Expression System (A29133, Thermo Fisher Scientific) and secreted into the medium. The culture supernatant was then collected and purified using a Protein A column (Ab-Capcher, Protenova) and a gel filtration column (Superdex 200 Increase, Cytiva). [Example 7 (1)] Analysis of anti-gpNMB antibody interactions by surface plasmon resonance 1: To compare the binding properties (binding rate and dissociation rate) of each anti-gpNMB antibody clone obtained in Example 1 to gpNMB, measurements were performed by surface plasmon resonance (SPR) under the following conditions. The measurement system used was a BIACORE T200 system. Anti-His monoclonal antibodies were immobilized to all flow cells of a CM5 sensor chip (BR-1005-30, Cytiva) at approximately 5,000 RU using an Amine Coupling Kit (BR-1000-50, GE) and a His Capture Kit (28-9950-56, Cytiva). HBS-EP+ (BR-1006-69, Cytiva) was used as the running buffer. Recombinant human gpNMB-FLAG-His (SEQ ID NO: 221) or recombinant mouse gpNMB-FLAG-His (SEQ ID NO: 223) was used as the ligand and captured in the measurement system. An anti-gpNMB antibody clone was used at a concentration of 100 nmol / L as the analyte. Shiga toxin 2 antibody (11E10) or control mouse IgG1 (leinco: Pro#M1411) was used as the analyte negative control. The temperature of the measurement system was set to 25°C. As a ligand, recombinant human gpNMB-FLAG-His was reacted with the anti-His monoclonal antibody in flow cell (2) with a target of 100 RU or less. Recombinant mouse gpNMB-FLAG-His was reacted with the anti-His monoclonal antibody in flow cell (4) with a target of 100 RU or less. At a flow rate of 20 μL / min, 10 nmol / L purified mouse IgG2a, κ, Isotype Ctrl, Clone: ​​MG2a-53 (401502, BioLegend, hereinafter Ctrl IgG2a) was reacted for 1 minute, and HBS-EP+ was allowed to flow for 10 minutes or more. The analyte was diluted with HBS-EP+ (100 nmol / L) and reacted with all flow cells for 600 seconds to obtain a binding curve, and then reacted with HBS-EP+ for 600 seconds to obtain a dissociation curve. After the reaction, regeneration buffer 1 (0.2% SDS), regeneration buffer 2 (100 mmol / L Tris-HCl (pH 8.5), 1 mol / L NaCl, 15 mmol / L MgCl ２ ) and regeneration buffer 3 (10 mmol / L glycine-HCl (pH 1.5)) for 1 minute each, and the gpNMB-FLAG-His from the measurement system was removed and washed. Using Biacore T200 Evaluation software (ver. 2.0), analysis was performed using a 1:1 binding model, and the binding rate value (Ass: 1 / Ms), binding stability value (Diss: 1 / s), and equilibrium dissociation value (Diss / Ass: M) were quantified as ordinal numbers. The results are shown in Table 7. [Example 7 (2)] Analysis of anti-gpNMB antibody interactions by surface plasmon resonance 2: Among the anti-gpNMB antibody clones obtained in Example 1, GPN05-1 and GPN06-1 were measured by surface plasmon resonance (SPR) to examine their concentration-dependent binding properties (binding rate and dissociation rate) to gpNMB. Specifically, the assay was carried out under the same conditions as in Example 7(1), except for the conditions described below. A CM3 sensor chip (BR-1005-36, Cytiva) was used, and various concentrations of anti-gpNMB antibody clones GPN05-1 and GPN06-1 were used as analytes. Single-cycle kinetics was used as the measurement condition. Each concentration of analyte was reacted for 450 seconds to obtain a binding curve, followed by a 600-second reaction with HBS-EP+ to obtain a dissociation curve. After the reaction was completed, the assay system was reacted with regeneration buffer 1 (0.2% SDS), regeneration buffer 2 (100 mmol / L Tris-HCl (pH 8.5), 1 mol / L NaCl, 15 mmol / L MgCl), and regeneration buffer 3 (10 mmol / L glycine-HCl (pH 1.5)) for 1 minute each. The gpNMB-FLAG-His protein was then removed from the assay system and washed. Using Biacore T200 Evaluation software (ver. 2.0), analysis was performed using a 1:1 binding model to calculate the dissociation rate constant (ka, 1 / Ms), binding rate constant (kd, 1 / s), and dissociation constant (KD, M). The results are shown in Table 8. [Example 8] Binding analysis of anti-gpNMB antibody (commercially available polyclonal antibody) in Alzheimer's disease model mice (APPosk mice): 21- to 25-month-old AP Posk mice were perfusion-fixed, and their brains were removed and prepared into 5-μm-thick paraffin sections. After deparaffinization, the brain sections were boiled in citrate buffer (pH 6) for 30 minutes to activate the antigens. They were then double-stained with commercially available anti-gpNMB polyclonal antibody AF2330 (2 μg / mL) + FITC-donkey anti-goat IgG antibody (Jackson Lab) and Iba1 antibody (WAKO, 5 μg / mL) + Rhodamine-donkey anti-rabbit IgG antibody (Jackson Lab). The sections were treated with the lipofuscin quencher TrueBlackplus (Biotium) for 10 minutes at room temperature and then mounted in DAPI-containing mounting medium (Vector). As a result, in brain sections from 21- to 25-month-old APPosk mice, cells staining with anti-gpNMB antibody (AF2330, R&D) were present among Iba1-positive microglia, and almost all gpNMB-positive cells were Iba1-positive microglia. Furthermore, microglia that had undergone morphological changes were gpNMB-positive microglia. These findings confirmed the appearance of gpNMB-positive microglia in Alzheimer's disease model mice (APPosk mice). [Example 9] Reduction of gpNMB-positive microglia by administration of anti-gpNMB antibodies (GPN05-1, GPN06-1) in Alzheimer's disease model mice (APPosk mice): AP Posk mice aged 19 to 20 months were divided into two groups (each group consisted of two males and three females), and each group was intraperitoneally administered a different anti-gpNMB antibody clone (GPN05-1, GPN06-1) obtained in Example 1 once a week for a total of five doses (1 mg / 400 μL each time in PBS). Four days after the final dose, the mice were perfusion-fixed, and the brains were removed and 5 μm-thick paraffin sections were prepared. After deparaffinization, brain sections were boiled in citrate buffer (pH 6) for 30 minutes to activate the antigen, followed by double staining with anti-mouse gpNMB goat polyclonal antibody (R&D systems, #AF2330, 2 μg / mL) + FITC-donkey anti-goat IgG antibody (Jackson Lab) and Iba1 antibody (WAKO, 5 μg / mL) + Rhodamine-donkey anti-rabbit IgG antibody (Jackson Lab). After treatment with lipofuscin quencher TrueBlackplus (Biotium) for 10 minutes at room temperature, sections were mounted in DAPI-containing mounting medium (Vector). One male in the GPN06-1-treated group died the week after the fourth administration. As a control, brain sections (from three AP Posk mice) aged 21 to 25 months were stained in the same manner. The resulting stained photographs are shown in Figure 2. Figure 2(A) shows the control, Figure 2(B) shows the GPN05-1 administration group, and Figure 2(C) shows the GPN06-1 administration group. As a result, in control AP Posk mice, numerous gpNMB-positive microglia (Iba1-positive) detected by anti-mouse gpNMB goat polyclonal antibody were observed in the hippocampus (CA2-CA3), entorhinal cortex (Ent), and dentate gyrus (DG). Meanwhile, gpNMB-positive microglia were reduced in the GPN05-1-treated group and were almost nonexistent in the GPN06-1-treated group. These results confirmed that administration of the anti-gpNMB monoclonal antibodies GPN05-1 and GPN06-1 reduced gpNMB-positive microglia in the brain. Furthermore, statistical analysis was performed on the immunostaining results. Specifically, the Iba1 staining signal and the gpNMB and Iba1 co-staining signal were extracted, and the area of ​​each stained region was quantified using the image processing software ImageJ. Graphs were created based on the obtained values. The resulting graph is shown in Figure 3. Significance tests were performed using StatView and a three-group ANOVA. Only those with a p-value of less than 0.05 by Fisher's PLSD were considered "significantly different," and the p-values ​​were recorded in the graph. These analytical results confirmed that administration of the anti-gpNMB monoclonal antibodies GPN05-1 and GPN06-1 resulted in a statistically significant reduction in gpNMB-positive microglia in the brain. This indicates that dysfunctional microglia, which constitute at least a portion of the gpNMB-positive microglia, were reduced. Furthermore, the reduction of dysfunctional microglia is supported by the results of removal of Aβ oligomers as shown in Example 10 below and restoration of synapse number as shown in Example 11 below. [Example 10] Removal of Aβ oligomers by administration of anti-gpNMB antibodies (GPN05-1, GPN06-1) in Alzheimer's disease model mice (APPosk mice): Nineteen- to twenty-month-old AP Posk mice were divided into two groups (two males and three females in each group). Each group received a different anti-gpNMB antibody (GPN05-1 or GPN06-1) obtained in Example 1 intraperitoneally once a week for a total of five doses (1 mg / 400 μL in PBS). Four days after the final dose, the mice were perfusion-fixed, their brains were removed, and 5 μm-thick paraffin sections were prepared. After deparaffinization, the brain sections were boiled in hydrochloric acid (pH 2) for 10 minutes and then stained with Aβ oligomer antibody 11A1 (IBL, 1 μg / mL) + Biotin-horse anti-mouse IgG antibody (Vector) + ABC elite (Vector) + DAB. As a control, brain sections (from three AP Posk mice) aged 21 to 25 months were stained in the same manner. The results are shown in Figure 4. Figure 4(A) shows the control, Figure 4(B) shows the GPN05-1 administration group, and Figure 4(C) shows the GPN06-1 administration group. As a result, Aβ oligomer-positive cells were observed in the hippocampus and dentate gyrus of control AP Posk mice. 11A1-positive cells decreased in the GPN05-1-treated group, and were almost absent in the GPN06-1-treated group. These results confirmed that administration of anti-gpNMB antibody eliminated Aβ oligomers in the brain. [Example 11] Synapse recovery by administration of anti-gpNMB antibodies (GPN05-1, GPN06-1) in Alzheimer's disease model mice (APPosk mice): Nineteen to twenty-month-old AP Posk mice were divided into two groups (two males and three females in each group). Each group received a different anti-gpNMB antibody (GPN05-1 or GPN06-1) obtained in Example 1 intraperitoneally once a week for a total of five doses (1 mg / 400 μL in PBS). Four days after the final dose, the mice were perfusion-fixed, their brains were removed, and 5 μm-thick paraffin sections were prepared. After deparaffinization, the brain sections were boiled in citrate buffer (pH 6) for 30 minutes and then stained with synaptophysin antibody SVP-38 (Sigma, 200-fold dilution) plus FITC-goat anti-mouse IgG antibody (Jackson Lab). Brain sections (two mice) from 20-month-old non-transgenic (Non-Tg) mice were stained in the same manner as Control 1, and brain sections (three mice) from 21- to 25-month-old AP Posk mice were stained in the same manner as Control 2. The resulting stained photographs are shown in Figure 5. Figure 5(A) shows Control 1 (Non-Tg mice), Figure 5(B) shows Control 2 (APPosk mice), Figure 5(C) shows the GPN05-1 administration group, and Figure 5(D) shows the GPN06-1 administration group. As a result, compared with control 1 non-transgenic (Non-Tg) mice, control 2 AP Posk mice showed a decrease in synaptophysin in hippocampal mossy fibers. Synaptophysin recovered slightly in the GPN05-1-treated group, while it recovered significantly in the GPN06-1-treated group. The recovery of synaptophysin appeared to correlate with the removal of Aβ oligomers. These results suggest that administration of anti-gpNMB antibodies increased the number of synapses in neurons in the brains of Alzheimer's disease model mice, restoring neuronal function. [Example 12-1] Evaluation of efficacy (removal of Aβ oligomers) by administration of anti-gpNMB antibodies (GPN09-1, GPN11-10, GPN15-2, GPN15-3, GPN18-2, 11E10) in Alzheimer's disease model mice (APPosk mice): AP Posk mice aged 19 to 20 months were divided into 6 groups (4 mice per group), and each group was intraperitoneally administered one of the different anti-gpNMB antibodies (GPN09-1, GPN11-10, GPN15-2, GPN15-3, GPN18-2) obtained in Example 1 and the control antibody 11E10 (anti-Shiga toxin mouse monoclonal antibody) once a week for a total of 5 times (1 mg / 400 μL each time in PBS). Four days after the final administration, the mice were perfusion-fixed, the brains were removed, and 5 μm-thick paraffin sections were prepared. After deparaffinization, the brain sections were boiled in hydrochloric acid (pH 2) for 10 minutes and then stained with Aβ oligomer antibody 11A1 (IBL, 1 μg / mL) + Biotin-horse anti-mouse IgG antibody (Vector) + ABC elite (Vector) + DAB. The resulting stained photographs are shown in Figure 6. Figure 6(A) shows the control antibody 11E10, Figure 6(B) shows the GPN09-1 administration group, Figure 6(C) shows the GPN11-10 administration group, Figure 6(D) shows the GPN15-2 administration group, Figure 6(E) shows the GPN15-3 administration group, and Figure 6(F) shows the GPN18-2 administration group. Furthermore, the immunostained photographs in Figure 6 were subjected to quantification of intracellular Aβ oligomer staining, and a significance test was performed using StatView and a three-group ANOVA. The results are shown in the graph in Figure 7. Only those with a p-value below 0.05 by Fisher's PLSD were considered "significantly different," and the p-values ​​are shown in the graph. As a result, in the AP Posk mice administered with the control antibody, 11A1 staining-positive cells were observed in the cerebral cortex. Meanwhile, 11A1 staining-positive cells decreased in the GPN09-1, GPN11-10, GPN15-2, and GPN15-3 administration groups, and were almost absent in the GPN18-2 administration group. These results confirmed that Aβ oligomers were removed from the brain by administration of anti-gpNMB antibodies. Furthermore, synaptophysin staining was performed on hippocampal slices from GPN18-2-treated AP Posk mice and non-Tg mice of approximately the same age according to the method of Example 11. The resulting stained photographs are shown in Figure 8. Figure 8(A) shows the control (non-Tg mice), and Figure 8(B) shows the GPN18-2-treated group. As a result, it was observed that the number of synapses in the hippocampus of GPN18-2-treated AP Posk mice had recovered to the non-Tg level. [Example 12-2] Evaluation of efficacy of administration of anti-gpNMB antibodies (GPN18-1, GPN18-6, GPN18-7) in Alzheimer's disease model mice (APPosk mice) (removal of Aβ oligomers): 18- to 20-month-old AP Posk mice were divided into three groups (five mice per group). Each group received a weekly intraperitoneal injection of a different anti-gpNMB antibody (GPN18-1, GPN18-6, or GPN18-7) obtained in Example 1 (1 mg / 400 μL in PBS). Four days after the final injection, the mice were perfusion-fixed, their brains were removed, and 5 μm-thick paraffin sections were prepared. After deparaffinization, the brain sections were boiled in hydrochloric acid (pH 2) for 10 minutes and then stained with Aβ oligomer antibody 11A1 (IBL, 1 μg / mL) + Biotin-horse anti-mouse IgG antibody (Vector) + ABC elite (Vector) + DAB. The resulting stained photographs are shown in Figure 9. Figure 9(A) shows the APPosk mouse non-administration control, Figure 9(B) shows the GPN18-1 administration group, Figure 9(C) shows the GPN18-6 administration group, and Figure 9(D) shows the GPN18-7 administration group. Furthermore, intracellular Aβ oligomer staining was quantified for the immunostained photographs in Figure 9, and significance testing was performed using StatView and a three-group ANOVA. The results are shown in the graph in Figure 10. Only results with a p-value below 0.05 by Fisher's PLSD were considered "significantly different," and the p-values ​​are shown in the graph. For statistical analysis, a "correction factor" was calculated for the untreated control, with the quantitative values ​​obtained from the animals used in this experiment equivalent to the average data of the four animals in the control antibody-administered group in Example 12-1. Graphs were created and statistical tests were performed using the corrected values ​​obtained by multiplying all quantitative values ​​obtained in this experiment by this factor. In the graph, the control was also replaced with the data from the four animals in the control antibody-administered group in Example 12-1. As a result, in the AP Posk mice treated with the control antibody, a large number of 11A1 staining-positive cells were observed in the cerebral cortex. On the other hand, in the GPN18-1 and GPN18-7 treated groups, the number of 11A1 staining-positive cells was statistically significantly reduced. A tendency for a decrease was also observed in the GPN18-6 treated group. These results demonstrate that the GPN18-1, GPN18-6, and GPN18-7 antibodies, which recognize PMEL-CAF-like regions, are effective in removing Aβ oligomers from the brain, similar to the GPN18-2 antibody. [Example 12-3] Evaluation of efficacy (removal of Aβ oligomers) by administration of anti-gpNMB antibodies (GPN18-2, GPN06-1, GPN18-5, 1-5E, anti-BTV mouse monoclonal antibody) in Alzheimer's disease model mice (APPosk mice): AP Posk mice aged 18 to 20 months were divided into five groups (five mice per group), and each group was intraperitoneally administered one of the different anti-gpNMB antibodies (GPN18-2, GPN06-1, GPN18-5, 1-5E) obtained in Example 1 and a control antibody (anti-BTV mouse monoclonal antibody (Leinco Technologies, Inc.)) once a week for a total of five doses (1 mg / 400 μL each time in PBS). Four days after the final dose, the mice were perfusion-fixed, the brains were removed, and 5 μm-thick paraffin sections were prepared. After deparaffinization, the brain sections were boiled in hydrochloric acid (pH 2) for 10 minutes and then stained with Aβ oligomer antibody 11A1 (IBL, 1 μg / mL) + Biotin-horse anti-mouse IgG antibody (Vector) + ABC elite (Vector) + DAB. The resulting stained photographs are shown in Figure 11. Figure 11(A) shows the control antibody, Figure 11(B) shows the GPN18-2 administration group, Figure 11(C) shows the GPN06-1 administration group, Figure 11(D) shows the GPN18-5 administration group, and Figure 11(E) shows the 1-5E administration group. Furthermore, the intracellular Aβ oligomer staining was quantified for the immunostained photographs in Figure 11, and a significance test was performed using StatView and a three-group ANOVA. The results are shown in the graph in Figure 12. Only those results for which the Fisher's PLSD p-value was less than 0.05 were considered to be "significantly different," and the p-values ​​were recorded in the graph. As a result, in the AP Posk mice administered with the control antibody, a large number of 11A1 staining-positive cells were observed in the cerebral cortex. Meanwhile, in the GPN18-2 and GPN06-1 administered groups, the number of 11A1 staining-positive cells was statistically significantly reduced. This reduction was also statistically significant compared to the GPN18-5 and 1-5E administered groups. These results demonstrate that the GPN18-2 antibody, which recognizes the PMEL-CAF-like region, and the GPN06-1 antibody, which recognizes the PKD region, are more effective in removing Aβ oligomers from the brain than the GPN18-5 antibody, which recognizes the N-terminal region, and the 1-5E antibody, which recognizes the vaccine peptide in the N-terminal region. The above comparative experiments demonstrated that antibodies recognizing the PMEL-CAF-like region and the PKD region are more effective than antibodies recognizing the N-terminal region in removing Aβ oligomers from the brain. [Reference Example 1] Generation of a novel Alzheimer's disease model mouse: We generated a novel Alzheimer's disease model mouse (Tg2576 / Tau264 mouse (APP / Tau-Tg)) by crossing Tg2576 mice (Swedish mutation APP introduced mice) that exhibit amyloid plaques with Tau264 mice that express human tau (wild-type). Pathological analysis of 9-month-old APP / Tau-Tg mice revealed amyloid plaque formation detected by anti-Aβ antibody and accumulation of phosphorylated tau detected by AT8 antibody. Furthermore, the appearance of gpNMB-positive microglia was confirmed by anti-gpNMB antibody (R&D, goat polyclonal antibody) and Iba1 antibody, which detects microglia. [Example 13] Evaluation of anti-gpNMB antibody for improvement of cognitive function in a novel Alzheimer's disease model mouse (APP / Tau-Tg): The cognitive function-improving effect of the anti-gpNMB antibody of the present invention was analyzed by the Morris water maze test using 14-month-old APP / Tau-Tg Alzheimer's disease model mice described in the Reference Examples. 14-month-old non-Tg (wild-type) mice born in the same litter were used as controls. <Group composition> Evaluated antibody group 1: anti-gpNMB mouse monoclonal antibody GPN06-1, 2.5 mg / mL in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine, was intraperitoneally administered in an amount of 0.4 mL once a week for a total of 5 times (n=8). Evaluated antibody group 2: anti-gpNMB mouse monoclonal antibody GPN18-2, 2.5 mg / mL in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine, was administered intraperitoneally in an amount of 0.4 mL once a week for a total of 5 times (n=7). Control antibody group: Anti-BTV mouse monoclonal antibody (Leinco Technologies, Inc.), 2.5 mg / mL in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine, was administered intraperitoneally in an amount of 0.4 mL once a week for a total of five doses (n=8). Non-Tg group: 0.4 mL of 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine was intraperitoneally administered once a week for a total of five times (n=12). <Water maze test> Preparation: A black pool with an inner diameter of 100 cm and a height of 45 cm was filled with water to a depth of 16 cm. The water temperature was adjusted to 21-23°C and kept colorless and transparent. After each trial day, feces were removed and approximately 10 L of water was replaced. Acquisition test: A 15 cm high transparent platform was submerged 20 cm from the wall (30 cm from the center). The area including the submerged platform was divided into four quadrants, and mice were randomly placed into one of the three quadrants without a platform. Five trials were conducted per day with a maximum duration of 60 seconds per trial. The interval between trials was approximately 5 minutes. The escape time required to reach the platform was recorded as data. Mice that did not escape within 60 seconds were manually guided to the platform by the operator, and the escape time was counted as 60 seconds. Mice on the platform were removed from the pool after 10 seconds and allowed to move freely until the next trial, after which their bodies were dried. The average escape time over the five trials was used to determine the performance of the mice on each day. The test was conducted for four days. When the performance of the control group (Non-Tg) became stable, the acquisition test was terminated, and a probe test was conducted the following day. Probe test: On the day following the final acquisition test, the platform was removed from the pool and 60 seconds of free swimming was recorded with a video camera. The video was observed, and the time spent by the free-swimming mice in the target quadrant was measured and expressed as a percentage of the 60 seconds. The significance test for each test was performed using Fisher's restricted least significant difference test (PLSD) for repeated measures, and Fisher's restricted least significant difference test (PLSD) for probe tests. The results of the acquisition test are shown in the graph in Figure 13. As a result of the analysis, the control antibody group to APP / Tau-Tg showed a significantly longer time to reach the hidden platform (escape latency) in the Morris water maze test compared to the non-Tg (wild-type) group. On the other hand, the group to which the anti-gpNMB antibody of the present invention, GPN06-1 or GPN18-2, was administered to APP / Tau-Tg showed a statistically significant shortening of the time to reach the hidden platform. The results of the probe test are shown in the graph in Figure 14. The results of the probe test were similar to those of the acquisition test. Specifically, the group administered with a control antibody to APP / Tau-Tg spent a statistically significant less time swimming around the quadrant where the hidden platform was located compared to the non-Tg (wild-type) group, and the groups administered with GPN06-1 or GPN18-2 spent a statistically significant longer time swimming around the quadrant where the hidden platform was located compared to the control antibody group. These results demonstrated that the anti-gpNMB antibodies GPN06-1 and GPN18-2 suppressed or reversed the decline in cognitive function in APP / Tau-Tg mice with statistically significant differences. [Example 14] Dose dependency of anti-gpNMB antibody in improving cognitive function in a novel Alzheimer's disease model mouse (APP / Tau-Tg) and pathological analysis: The dose dependency of the cognitive function-improving effect of the anti-gpNMB antibody of the present invention was analyzed by the Morris water maze test using 14-month-old Alzheimer's disease model mice APP / Tau-Tg described in Example 13. 14-month-old non-Tg (wild-type) mice born in the same litter were used as controls. <Group composition> Evaluated antibody group 1: A solution of anti-gpNMB mouse monoclonal antibody GPN18-2 at a concentration of 0.25 mg / mL in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine was administered intraperitoneally in an amount of 0.4 mL once a week for a total of five times (n=7). Evaluated antibody group 2: A solution of anti-gpNMB mouse monoclonal antibody GPN18-2 at a concentration of 2.5 mg / mL in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine was administered intraperitoneally in an amount of 0.4 mL once a week for a total of five times (n=7). Control antibody group: A 2.5 mg / mL solution of anti-BTV mouse monoclonal antibody (Leinco Technologies, Inc.) in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine was administered intraperitoneally in an amount of 0.4 mL once a week for a total of five doses (n=6). Non-Tg group: 0.4 mL of 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine was administered intraperitoneally once a week for a total of five times (n=12). <Water maze test> Preparation: A black pool with an inner diameter of 100 cm and a height of 45 cm was filled with water to a depth of 16 cm. The water temperature was adjusted to 21-23°C and kept colorless and transparent. After each trial day, feces were removed and approximately 10 L of water was replaced. Acquisition test: A 15 cm high transparent platform was submerged 20 cm from the wall (30 cm from the center). The area including the submerged platform was divided into four quadrants, and mice were randomly placed into one of the three quadrants without a platform. Five trials were conducted per day with a maximum duration of 60 seconds per trial. The interval between trials was approximately 5 minutes. The escape time required to reach the platform was recorded as data. Mice that did not escape within 60 seconds were manually guided to the platform by the operator, and the escape time was counted as 60 seconds. Mice on the platform were removed from the pool after 10 seconds and allowed to move freely until the next trial, after which their bodies were dried. The average escape time over the five trials was used to determine the performance of the mice on each day. The test was conducted for four days. When the performance of the control group (Non-Tg) became stable, the acquisition test was terminated, and a probe test was conducted the following day. Probe test: On the day following the final acquisition test, the platform was removed from the pool and 60 seconds of free swimming was recorded with a video camera. The video was observed, and the time spent by the free-swimming mice in the target quadrant was measured and expressed as a percentage of the 60 seconds. The significance test for each test was performed using Fisher's restricted least significant difference test (PLSD) for repeated measures, and Fisher's restricted least significant difference test (PLSD) for probe tests. The results of the acquisition test are shown in the graph in Figure 15. As a result of the analysis, the control antibody group to APP / Tau-Tg showed a significantly longer time to reach the hidden platform (escape latency) in the Morris water maze test compared to the non-Tg (wild-type) group. On the other hand, the group to which APP / Tau-Tg was administered 1 mg / head of the anti-gpNMB antibody of the present invention, GPN18-2, showed a statistically significant reduction in the time to reach the hidden platform. Furthermore, the group to which 0.1 mg / head of GPN18-2 was administered showed a tendency for the time to reach the hidden platform to be shortened. The results of the probe test are shown in the graph in Figure 16. The results of the probe test were similar to those of the acquisition test. Specifically, the group administered with a control antibody to APP / Tau-Tg spent a statistically significantly less time swimming around the quadrant where the hidden platform was located compared to the non-Tg (wild-type) group, and the group administered with 1 mg / head of GPN18-2 spent a statistically significantly longer time swimming around the quadrant where the hidden platform was located compared to the control antibody group. Furthermore, the group administered with 0.1 mg / head of GPN18-2 showed a tendency to spend a longer time swimming around the quadrant where the hidden platform was located. These results demonstrate that the anti-gpNMB antibody GPN18-2 dose-dependently inhibits or reverses the decline in cognitive function in APP / Tau-Tg mice. <Pathological analysis> Anti-gpNMB antibody: 14-month-old APP / Tau-Tg mice administered 1 mg / head of GPN18-2 or 1 mg / head of a control antibody (control) were perfusion-fixed, and their brains were removed and prepared into 5-μm-thick paraffin sections. After deparaffinization, the brain sections were boiled in citrate buffer (pH 6) for 30 minutes to activate the antigens, and then double-stained with anti-gpNMB antibody AF2330 (R&D, 2 μg / mL) + FITC-donkey anti-goat IgG antibody (Jackson Lab) and anti-Iba1 antibody (WAKO, 5 μg / mL) + rhodamine-donkey anti-rabbit IgG antibody (Jackson Lab). After treatment with lipofuscin quencher True Black plus (Biotium) at room temperature for 10 minutes, the sections were mounted with DAPI-containing mounting medium (Vector). The results of staining the hippocampus and entorhinal cortex are shown in Figure 17. Staining for Aβ and phosphorylated tau was also performed simultaneously. Brain sections were boiled in hydrochloric acid (pH 2) for 10 minutes and then double-stained with AT8 (phosphorylated tau, Invitrogen #MN1020) antibody + FITC-goat anti-mouse IgG antibody (Jackson Lab) and anti-Aβ antibody β001 (Aβ, Rb pAb: Lab-made) + rhodamine-goat anti-rabbit IgG antibody (Jackson Lab). After treatment with lipofuscin quencher True Black plus (Biotium) for 10 minutes at room temperature, sections were mounted in DAPI-containing mounting medium (Vector). The results of staining the hippocampus and entorhinal cortex are shown in Figure 18. Furthermore, neurofibrillary tangles (NFTs) were detected by Gallius silver staining. The results showed that NFT formation was suppressed in 14-month-old APP / Tau-Tg mice administered 1 mg / head of GPN18-2 compared to 14-month-old APP / Tau-Tg mice administered 1 mg / head of the control antibody. The results are shown in Figure 19. [Example 15] Humanization design of mouse anti-gpNMB antibody: GPN06-1: Based on the amino acid sequence of the anti-gpNMB antibody GPN06-1, the CDR regions were identified using IMGT (Lefranc, M.-P., Pommie, C., Ruiz, M., Giudicelli, V., Foulquier, E., Truong, L., Thouvenin-Contet, V. and Lefranc, G. "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains", Dev. Comp. Immunol., 27, 55-77 (2003) PMID: 12477501 LIGM:268.) and Kabat numbering. The combined IMGT / Kabat method was used to optimize the CDR loop structure. <Heavy chain humanization design> The human germline gene most similar to the amino acid sequence of the mouse heavy chain variable region (GPN06-1_VH) (SEQ ID NO: 29) was IGHV1-46*01. Using a BLAST search, 200 human IgG sequences highly homologous to GPN06-1_VH were selected as candidates. Four framework sequences were then ultimately selected from the perspectives of framework homology, retention of key amino acids in the framework, and loop structure. CDR grafting was performed on these sequences to create humanized mutant sequences hGPN06-1_VH1, hGPN06-1_VH2, hGPN06-1_VH3, and hGPN06-1_VH4. Furthermore, a humanized mutant sequence hGPN06-1_VH5 was created by CDR grafting using the IGHV1-46*01 sequence as a framework. The alignment of these humanized mutant sequences hGPN06-1_VH1 to VH5 with mouse GPN06-1_VH is shown in Figure 20. The underlined regions are the identified CDR regions. Table 9 also shows the identity and homology of these humanized mutant sequences hGPN06-1_VH1 to VH5 with mouse sequence GPN06-1_VH. When the humanized mutant sequences hGPN06-1_VH1 to VH5 are arranged in descending order of identity and homology to mouse GPN06-1_VH, the order was VH3 = VH5 > VH2 > VH1 > VH4. <Light chain humanized design> The human germline gene most similar to the amino acid sequence of the mouse light chain variable region (GPN06-1_VL) (SEQ ID NO: 31) was IGKV1-9*01. Using a BLAST search, 200 human IgK sequences highly homologous to GPN06-1_VL were selected as candidates. Four framework sequences were then ultimately selected from the perspectives of framework homology, retention of key amino acids in the framework, and loop structure. CDR grafting was performed on these sequences to obtain the humanized mutant sequences hGPN06-1_VL1, hGPN06-1_VL2, hGPN06-1_VL3, and hGPN06-1_VL4. Furthermore, a humanized mutant sequence hGPN06-1_VL5 was obtained by CDR grafting using the IGKV1-9*01 sequence as a framework. The alignment of these humanized mutant sequences hGPN06-1_VL1 to VL5 with mouse GPN06-1_VL is shown in Figure 21. The underlined regions are the identified CDR regions. Table 10 also shows the identity and homology of these humanized mutant sequences hGPN06-1_VL1 to VL5 with mouse sequence GPN06-1_VL. The humanized mutant sequences hGPN06-1_VL1 to VL5 were ranked in descending order of identity and homology to mouse GPN06-1_VL, as follows: VL5 > VL4 > VL1 > VL3 > VL2. [Example 16] Selection of GPN06-1 humanized antibody 25 types of humanized antibodies were prepared by combining five types of humanized heavy chain sequences and five types of humanized light chain sequences of the anti-gpNMB antibody GPN06-1 designed in Example 15. The binding activity of these humanized antibodies was evaluated by antigen ELISA, and humanized antibodies with binding activity similar to that of human chimeric antibodies were selected. Specifically, a gene sequence encoding the H chain and L chain of the humanized anti-gpNMB antibody designed in Example 15, each with a gene sequence encoding a signal sequence added to the 5' end, was inserted into the animal cell expression vector pcDNA3.4 to prepare a plasmid, and transient expression was carried out using an ExpiCHO Expression System (A29133, Thermo Fisher Scientific) to secrete the antibody into the medium. The culture supernatant was then collected and purified using a Protein A column (Ab-Capcher, Protenova) and a gel filtration column (Superdex 200 Increase, Cytiva). Antigen ELISA was performed by adding serially diluted purified humanized antibody solutions to a plate onto which recombinant human soluble gpNMB (SEQ ID NO: 221) was immobilized. The results are shown in Table 11. As a result, hGPN06-1_H1L1, hGPN06-1_H1L2, hGPN06-1_H2L1, hGPN06-1_H2L2, hGPN06-1_H3L1, hGPN06-1_H3L2, hGPN06-1_H4L1, hGPN06-1_H5L2, hGPN06-1_H5L4, and hGPN06-1_H5L5 had binding affinity at a level equivalent to that of the human chimeric antibody (hGPN06-1_H0L0) (EC ５０ The values ​​were found to be within 3-fold of those of the chimeric antibody hGPN06-1_H0L0. [Example 17] Analysis of interaction of GPN06-1 humanized anti-gpNMB antibody by surface plasmon resonance 3: Of the humanized GPN06 antibody variants obtained in Example 16, hGPN06-1_H1L1, hGPN06-1_H1L2, hGPN06-1_H1L4, hGPN06-1_H2L1, hGPN06-1_H2L2, hGPN06-1_H3L1, hGPN06-1_H3L2, hGPN06-1_H4L1, and hGPN06-1_H5L2 were measured by surface plasmon resonance (SPR) to compare their binding properties (binding rate and dissociation rate) to human soluble gpNMB (SEQ ID NO: 221). Specifically, measurement and analysis conditions were the same as those in Example 7, except for the conditions described below. The analytes used were human chimeric antibody hGPN06-1_H0L0 and humanized GPN06 antibody variants hGPN06-1_H1L1, hGPN06-1_H1L2, hGPN06-1_H1L4, hGPN06-1_H2L1, hGPN06-1_H2L2, hGPN06-1_H3L1, hGPN06-1_H3L2, hGPN06-1_H4L1, and hGPN06-1_H5L2. Each concentration of analyte was reacted for 600 seconds to obtain a binding curve, and then HBS-EP+ was reacted for 1200 seconds to obtain a dissociation curve. After the reaction was completed, the mixture was reacted with renaturation buffer 1 (0.2% SDS), renaturation buffer 2 (100 mmol / L Tris-HCl (pH 8.5), 1 mol / L NaCl, 15 mmol / L MgCl2), and renaturation buffer 3 (10 mmol / L glycine-HCl (pH 1.5)) for 1 minute each, and the gpNMB-FLAG-His from the measurement system was removed and washed. Using BIACORE T200 Evaluation software (ver. 2.0), analysis was performed using a 1:1 Binding Model, and the dissociation rate constant (ka, 1 / Ms), binding rate constant (kd, 1 / s), and dissociation constant (KD, M) were calculated. The results are shown in Table 12. [Example 18] Identification of CDR region amino acids important for binding by alanine substitution of GPN06-1 humanized antibody Sixty-five CDR-substituted variants of the humanized anti-gpNMB antibody hGPN06-1_H1L1 prepared in Example 16 were prepared by substituting amino acids in the CDR regions with alanine. The binding of these alanine-substituted antibodies to recombinant human soluble gpNMB (SEQ ID NO: 221) was evaluated by antigen ELISA to identify the amino acids in the CDR-grafted region that are important for binding. The alanine-substituted variants of the humanized anti-gpNMB antibody hGPN06-1_H1L1 prepared and the measurement results of binding activity are shown in Tables 13 and 14 below. From the results obtained, the amino acids whose binding activity was reduced by alanine substitution in each CDR region were determined to be: isoleucine at position 29, tyrosine at position 31, and histidine at position 33 in CDR-grafting region-L1 (SEQ ID NO: 277) of the light chain variable region of humanized anti-gpNMB antibody hGPN06-1_H1L1 (SEQ ID NO: 297); threonine at position 50 in CDR-grafting region-L2 (SEQ ID NO: 279); histidine at position 88, glutamine at position 89, tryptophan at position 90, serine at position 92, tyrosine at position 93, proline at position 94, and cysteine ​​at position 95 in CDR-grafting region-L3 (SEQ ID NO: 281); and In addition, the following residues were identified as being extremely important for maintaining binding: tyrosine at position 27, asparagine at position 32, and tryptophan at position 33 in CDR-grafting region-H1 (SEQ ID NO: 271); aspartic acid at position 55, phenylalanine at position 57, threonine at position 58, asparagine at position 59, tyrosine at position 60, and asparagine at position 61 in CDR-grafting region-H2 (SEQ ID NO: 273); and arginine at position 98, glycine at position 100, and glycine at position 109 in CDR-grafting region-H3 (SEQ ID NO: 275) in the heavy-chain variable region of humanized anti-gpNMB antibody hGPN06-1_H1L1 (SEQ ID NO: 295). [Example 19] Humanization design of mouse anti-gpNMB antibody: GPN18-2: Based on the amino acid sequence of the anti-gpNMB antibody GPN18-2, the CDR regions were identified using IMGT (Lefranc, M.-P., Pommie, C., Ruiz, M., Giudicelli, V., Foulquier, E., Truong, L., Thouvenin-Contet, V. and Lefranc, G. "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains", Dev. Comp. Immunol., 27, 55-77 (2003) PMID: 12477501 LIGM:268.) and Kabat numbering. The combined IMGT / Kabat method was used to optimize the CDR loop structure. <Heavy chain humanization design> The human germline gene most similar to the amino acid sequence of the mouse heavy chain variable region (GPN18-2_VH) ​​(SEQ ID NO: 141) was IGHV2-05*09. Using a BLAST search, 200 human IgG sequences highly homologous to GPN18-2_VH were selected as candidates. Four framework sequences were then ultimately selected from the perspectives of framework homology, retention of key amino acids in the framework, and loop structure. CDR grafting was performed on these sequences to create humanized mutant sequences hGPN18-2_VH1, hGPN18-2_VH2, hGPN18-2_VH3, and hGPN18-2_VH4. Furthermore, a humanized mutant sequence hGPN18-2_VH5 was created by CDR grafting using the IGHV2-05*09 sequence as a framework. The alignment of these humanized mutant sequences VH1 to VH5 with mouse GPN18-2_VH is shown in Figure 22. The underlined regions are the identified CDR-grafted regions. Table 15 below shows the identity and homology of these humanized mutant sequences hGPN18-2_VH1 to VH5 with mouse sequence GPN18-2_VH. The humanized mutant sequences hGPN18-2_VH1 to VH5 were ranked in descending order of identity and homology to mouse GPN18-2_VH, as follows: VH5 > VH3 > VH1 > VH2 > VH4. <Light chain humanized design> The human germline gene most similar to the amino acid sequence of the mouse light chain variable region (GPN18-2_VL) (SEQ ID NO: 143) was IGKV2-30*01. Meanwhile, 200 human IgK sequences highly homologous to GPN18-2_VL were selected as candidates using a BLAST search. Four framework sequences were then ultimately selected from the perspectives of framework homology, retention of key amino acids in the framework, and loop structure. CDR grafting was performed on these sequences to obtain the humanized mutant sequences hGPN18-2_VL1, hGPN18-2_VL2, hGPN18-2_VL3, and hGPN18-2_VL4. Furthermore, a humanized mutant sequence hGPN18-2_VL5 was obtained by CDR grafting using the IGKV2-30*01 sequence as a framework. The alignment of these humanized mutant sequences hGPN18-2_VL1 to VL5 with mouse GPN18-2_VL is shown in Figure 23. The underlined regions are the identified CDR-grafted regions. Table 16 below shows the identity and homology of these humanized mutant sequences hGPN18-2_VL1 to VL5 with mouse sequence GPN18-2_VL. The humanized mutant sequences hGPN18-2_VL1 to VL5 were ranked in descending order of identity and homology to mouse GPN18-2_VL, as follows: VL5 > VL1 > VL2 > VL3 > VL4. [Example 20] Selection of GPN18-2 humanized antibody Twenty-five humanized antibodies were prepared by combining five humanized heavy chain sequences and five humanized light chain sequences of the anti-gpNMB antibody GPN18-2 designed in Example 19. The binding activity of these humanized antibodies was evaluated by antigen ELISA, and humanized antibodies with binding activity similar to that of the human chimeric antibody hGPN18-2_H0L0 were selected. Specifically, a gene sequence encoding the H chain and L chain of the humanized anti-gpNMB antibody designed in Example 19, each with a gene sequence encoding a signal sequence added to the 5' end, was inserted into the animal cell expression vector pcDNA3.4 to prepare a plasmid, and transient expression was carried out using an ExpiCHO Expression System (A29133, Thermo Fisher Scientific) to secrete the antibody into the medium. The culture supernatant was then collected and purified using a Protein A column (Ab-Capcher, Protenova) and a gel filtration column (Superdex 200 Increase, Cytiva). Antigen ELISA was performed by adding serially diluted purified humanized antibody solutions to a plate onto which recombinant human soluble gpNMB (SEQ ID NO: 221) was immobilized. The results are shown in Table 17 below. As a result, hGPN18-2_H1L3, hGPN18-2_H1L4, hGPN18-2_H2L3, hGPN18-2_H2L4, hGPN18-2_H2L5, hGPN18-2_H3L3, hGPN18-2_H3L4, hGPN18-2_H5L3, and hGPN18-2_H5L4 had binding affinity at a level equivalent to that of the human chimeric antibody (hGPN18-2_H0L0) (EC ５０ The values ​​were found to be within 3-fold of those of the human chimeric antibody hGPN18-2_H0L0. [Example 21] Analysis of interaction between GPN18-2 and humanized anti-gpNMB antibody by surface plasmon resonance: The binding properties (binding rate and dissociation rate) of the 25 humanized GPN18-2 antibodies obtained in Example 20 to human gpNMB were measured by surface plasmon resonance (SPR) to compare them. Specifically, the measurement and analysis conditions were the same as those in Example 7, except for the conditions described below. The temperature of the measurement system was set to 36°C. The humanized GPN18-2 antibody prepared in Example 20 was used as the analyte. The analyte was diluted with HBS-EP+ (100 nmol / L) and reacted with all flow cells for 300 seconds to obtain a binding curve, followed by a 300-second reaction with HBS-EP+ to obtain a dissociation curve. After the reaction was completed, the cells were reacted with regeneration buffer 1 (0.2% SDS), regeneration buffer 2 (100 mmol / L Tris-HCl (pH 8.5), 1 mol / L NaCl, 15 mmol / L MgCl), and regeneration buffer 3 (10 mmol / L glycine-HCl (pH 1.5)) for 1 minute each, and the gpNMB-FLAG-His from the measurement system was removed and washed. Using BIACORE T200 Evaluation software (ver. 2.0), the data were analyzed using a 1:1 binding model, and the binding rate (Ass: 1 / Ms), binding stability (Diss: 1 / s), and equilibrium dissociation (Diss / Ass: M) were quantified as ordinal numbers. The results are shown in Table 18. [Example 22] Identification of CDR region amino acids important for binding by alanine substitution of GPN18-2 humanized antibody Seventy-four CDR-substituted variants of the humanized anti-gpNMB antibody hGPN18-2_H2L3 prepared in Example 20 were prepared by substituting amino acids in the CDR regions with alanine. The binding of these alanine-substituted antibodies to recombinant human soluble gpNMB (SEQ ID NO: 221) was evaluated by antigen ELISA to identify the amino acids in the CDR-grafted region that are important for binding. The alanine-substituted variants of the humanized anti-gpNMB antibody hGPN18-2_H2L3 prepared and the measurement results of their binding activity are shown in Tables 19 and 20 below. From the results obtained, it was found that the amino acids whose binding activity was reduced by alanine substitution in each CDR region were: leucine at position 31, tyrosine at position 37, and glutamic acid at position 39 in CDR-grafting region-L1 (SEQ ID NO: 305) of the light chain variable region of humanized anti-gpNMB antibody hGPN18-2_H2L3 (SEQ ID NO: 325); lysine at position 55 in CDR-grafting region-L2 (SEQ ID NO: 307); phenylalanine at position 94 in CDR-grafting region-L3 (SEQ ID NO: 309); and the humanized In the heavy chain variable region (SEQ ID NO: 323) of the anti-gpNMB antibody hGPN18-2_H2L3, the following residues were identified as being critically important for maintaining binding: aspartic acid at position 52, tryptophan at position 54, aspartic acid at position 58, and proline at position 63 in the CDR-grafting region-H2 (SEQ ID NO: 301); and arginine at position 99, threonine at position 100, tyrosine at position 102, tyrosine at position 105, tyrosine at position 107, and methionine at position 110 in the CDR-grafting region-H3 (SEQ ID NO: 303). [Reference Example 2] Examination of microglia in Parkinson's disease model mice <Pathological analysis> A 14-month-old A53T mutant human α-synuclein Tg mouse was perfusion-fixed, and the brain was removed and prepared into 5 μm-thick paraffin sections. After deparaffinization, the brain sections were boiled in citrate buffer (pH 6) for 30 minutes to activate the antigens, and then double-stained with anti-gpNMB antibody AF2330 (R&D, 2 μg / mL) + FITC-donkey anti-goat IgG antibody (Jackson Lab) and anti-Iba1 antibody (WAKO, 5 μg / mL) + rhodamine-donkey anti-rabbit IgG antibody (Jackson Lab). The results are shown in Figure 24. [Example 23] Analysis of cognitive function improvement in Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) by anti-gpNMB antibodies The anti-gpNMB antibody of the present invention was administered to 8-9 month old A53T mutant human α-synuclein transgenic mice once a week for a total of 5 doses, and the cognitive function improvement effect after administration was analyzed using the Morris water maze test. Non-transgenic (wild-type) mice aged 9-10 months born from the same litter were used as controls. <Group composition> Evaluated antibody group 1: anti-gpNMB mouse monoclonal antibody GPN06-1, 2.5 mg / mL in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine, was intraperitoneally administered in an amount of 0.4 mL once a week for a total of 5 times (n=10). Evaluated antibody group 2: anti-gpNMB mouse monoclonal antibody GPN18-2, 2.5 mg / mL in 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine, was administered intraperitoneally in an amount of 0.4 mL once a week for a total of five times (n=9). - αSyn-Tg group: 0.4 mL of 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine was administered intraperitoneally once a week for a total of 5 times (n=10). Non-Tg group: 0.4 mL of 150 mM NaCl buffer (pH 6.5) containing 0.02 M histidine was intraperitoneally administered once a week for a total of five times (n=12). <Water maze test> Preparation: A black pool with an inner diameter of 100 cm and a height of 45 cm was filled with water to a depth of 16 cm. The water temperature was adjusted to 21-23°C and kept colorless and transparent. After each trial day, feces were removed and approximately 10 L of water was replaced. Acquisition test: A 15 cm high transparent platform was submerged 20 cm from the wall (30 cm from the center). The area including the submerged platform was divided into four quadrants, and mice were randomly placed into one of the three quadrants without a platform. Five trials were conducted per day with a maximum duration of 60 seconds per trial. The interval between trials was approximately 5 minutes. The escape time required to reach the platform was recorded as data. Mice that did not escape within 60 seconds were manually guided to the platform by the operator, and the escape time was counted as 60 seconds. Mice on the platform were removed from the pool after 10 seconds and allowed to move freely until the next trial, after which their bodies were dried. The average escape time over the five trials was used to determine the performance of the mice on each day. The test was conducted for four days. When the performance of the Non-Tg group became stable, the acquisition test was terminated, and a probe test was conducted the next day. Probe test: On the day following the final acquisition test, the platform was removed from the pool and 60 seconds of free swimming was recorded with a video camera. The video was observed, and the time spent by the free-swimming mice in the target quadrant was measured and expressed as a percentage of the 60 seconds. The significance test for each test was performed using Fisher's restricted least significant difference test (PLSD) for repeated measures, and Fisher's restricted least significant difference test (PLSD) for probe tests. The results of the acquisition test are shown in the graph in Figure 25. The analysis results showed that the αSyn-Tg (A53T mutant human α-synuclein-Tg mice) group had a significantly longer escape latency in the Morris water maze test compared to the non-Tg (littermate wild-type mice) group. On the other hand, the group of A53T mutant human α-synuclein-Tg mice administered with the anti-gpNMB antibodies GPN06-1 or GPN18-2 of the present invention showed a statistically significant reduction in the escape latency. Example 24: Analysis of the suppression of motor dysfunction by anti-gpNMB antibodies in Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) To evaluate the therapeutic effect of anti-gpNMB antibody on the motor function of Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice), the mice that had undergone cognitive function evaluation in the Morris water maze test in Example 23 were used to evaluate motor function the following week. No motor disorders were observed during the Morris water maze test. <Rotarod test> Motor function was assessed by a rotarod test using a MK-610A rotarod treadmill for mice (Muromachi Kikai, Tokyo, Japan). On the first day, mice were trained to stay on the rod rotating at 5 rpm for 180 s. Next, the rotation speed was increased from 4 rpm to 40 rpm over 240 s, and this accelerating rotarod training was repeated twice. The next day, the accelerating rotarod test was performed twice with an interval of 1 h, and the time it took for the mouse to fall off the rod was recorded. If the mouse clung to the rod and rotated completely downward, it was considered to have fallen off the rod. The average time for the two trials was calculated and graphed (Figure 26). <Inverted screen test> Following the rotarod test, the mice were further evaluated for motor strength and coordination using the inverted screen test. Mice were individually placed on a circular wire screen (24 cm diameter, 1.2 cm × 1.2 cm opening) mounted horizontally on a metal rod. The screen was then rotated 180°, and the mice's behavior was observed for 2 minutes. The time it took for the mice to fall off the screen was recorded. If the mice climbed to the top of the screen or remained clinging to the bottom of the screen, a waiting time of 120 seconds was assigned. The average time for two trials was calculated and plotted graphically (Figure 27). [Example 25] Pathological analysis of Parkinson's disease model mice (A53T mutant human α-synuclein-Tg mice) administered with anti-gpNMB antibody <Pathological analysis> Anti-gpNMB antibody: Nine- to ten-month-old A53T mutant human α-synuclein Tg mice administered 1 mg / head of GPN18-2 or GPN06-1, and 9- to 10-month-old A53T mutant human α-synuclein Tg mice (control) administered vehicle, were perfusion-fixed, and their brains were removed and prepared into 5-μm-thick paraffin sections. After deparaffinization, the brain sections were boiled in citrate buffer (pH 6) for 30 minutes to activate the antigen, and then double-stained with anti-gpNMB antibody AF2330 (R&D, 2 μg / mL) + FITC-donkey anti-goat IgG antibody (Jackson Lab) and Iba1 antibody (WAKO, 5 μg / mL) + rhodamine-donkey anti-rabbit IgG antibody (Jackson Lab). After treatment with lipofuscin quencher True Black plus (Biotium) at room temperature for 10 minutes, the sections were mounted with DAPI-containing mounting medium (Vector). The staining results are shown in Figure 28. Furthermore, statistical analysis was performed on the above immunostaining results. Specifically, the co-stained signals of gpNMB (AF2330) and Iba1 were extracted, and the area of ​​each stained region was quantified using the image processing software ImageJ. Graphs were created based on the obtained values. The resulting graph is shown in Figure 29. Significance tests were performed using StatView and a three-group ANOVA. Only those with a p-value of less than 0.05 by Fisher's PLSD were considered "significantly different," and the p-values ​​were listed in the graph. These analytical results confirmed that administration of the anti-gpNMB monoclonal antibodies GPN18-2 and GPN06-1 resulted in a statistically significant reduction in gpNMB-positive microglia in the brain. This indicates that dysfunctional microglia, which comprise at least a portion of gpNMB-positive microglia, were reduced. Furthermore, the fact that the reduction of dysfunctional microglia improved the pathological condition is supported by the removal of synuclein oligomers and phosphorylated synuclein, as well as the suppression or recovery of the decline in synapse number, as described below. Staining for phosphorylated α-synuclein, α-synuclein oligomers, and synaptophysin was also performed simultaneously. Brain sections were boiled in 10 mM hydrochloric acid (pH 2) for 10 minutes and then reacted with [pSer129] α-synuclein rabbit monoclonal antibody (Abcam-Epitomics, Cambridge, UK). Separately, sections were boiled in 10 mM citrate buffer (pH 6) for 30 minutes and then reacted with antibodies against α-synuclein oligomers (Syn33; Merck Millipore, Darmstadt, Germany) and synaptophysin (SVP-38; Sigma-Aldrich). For synuclein staining, the sections were then reacted with a biotinylated secondary antibody, an HRP-labeled avidin-biotin complex, and diaminobenzidine (DAB) to develop color. Synaptophysin was stained with FITC-goat anti-mouse IgG antibody (Jackson Lab). After treatment with lipofuscin quencher True Black plus (Biotium) for 10 minutes at room temperature, the sections were mounted with DAPI-containing mounting medium (Vector). The results of staining for phosphorylated α-synuclein, α-synuclein oligomers, and synaptophysin are shown in Figures 30, 32, and 34, respectively. Furthermore, statistical analysis was performed on the above immunostaining results. Specifically, the staining signals of phosphorylated α-synuclein, α-synuclein oligomers, and synaptophysin were each extracted, and the area of ​​each stained region was quantified using the image processing software ImageJ. Graphs were created based on the obtained values. The resulting graphs for phosphorylated α-synuclein, α-synuclein oligomers, and synaptophysin are shown in Figures 31, 33, and 35, respectively. Significance tests were performed using StatView, with analysis performed by three-group ANOVA. Only those with a p-value of less than 0.05 by Fisher's PLSD were considered "significantly different," and the p-values ​​were noted in the graphs. The present invention can provide antibodies that specifically bind to microglia that express vertebrate gpNMB, thereby eliminating dysfunctional microglia, promoting the removal of toxic proteins such as amyloid β oligomers and / or phosphorylated tau and / or synuclein oligomers, restoring the number of synapses, and / or inhibiting or restoring decline in cognitive function and motor function. Therefore, the present invention can be used for the treatment, prevention, or diagnosis of neurodegenerative diseases in which microglia are involved, such as Alzheimer's disease and Parkinson's disease. SEQ ID NO: 1 Sequence Name: Antibody GPN05-1 CDR-H1 Sequence Type: AA Organism Name: Mus musculus GYAFSNHL SEQ ID NO: 2 Sequence Name: Antibody GPN05-1 CDR-H1 Sequence Type: DNA Organism Name: synthetic construct GGCTACGCCTTCAGCAACCACCTG SEQ ID NO: 3 Sequence Name: Antibody GPN05-1 CDR-H2 Sequence Type: AA Organism Name: Mus musculus INPGSGGT SEQ ID NO: 4 Sequence Name: Antibody GPN05-1 CDR-H2 Sequence Type: DNA Organism Name: synthetic construct ATCAACCCTGGCAGCGGCGGCACC SEQ ID NO: 5 Sequence Name: Antibody GPN05-1 CDR-H3 Sequence Type: AA Organism Name: Mus musculus ARGANWDVGFAY SEQ ID NO: 6 Sequence Name: Antibody GPN05-1 CDR-H3 Sequence Type: DNA Organism Name: synthetic construct GCTAGAGGCGCTAATTGGGACGTGGGGTTCGCGTAT SEQ ID NO: 7 Sequence Name: Antibody GPN05-1 CDR-L1 Sequence Type: AA Organism Name: Mus musculus QDIVKN SEQ ID NO: 8 Sequence Name: Antibody GPN05-1 CDR-L1 Sequence Type: DNA Organism Name: synthetic construct CAAGACATCGTGAAGAAC SEQ ID NO: 9 Sequence Name: Antibody GPN05-1 CDR-L2 Sequence Type: AA Organism Name: Mus musculus YAT SEQ ID NO: 10 Sequence Name: Antibody GPN05-1 CDR-L2 Sequence Type: DNA Organism Name: synthetic construct TACGCCACC SEQ ID NO: 11 Sequence Name: Antibody GPN05-1 CDR-L3 Sequence Type: AA Organism Name: Mus musculus LQFHEFPRT SEQ ID NO: 12 Sequence Name: Antibody GPN05-1 CDR-L3 Sequence Type: DNA Organism Name: synthetic construct CTGCAGTTCCACGAGTTCCCTAGAACC SEQ ID NO: 13 Sequence Name: Antibody GPN05-1 VH Sequence Type: AA Organism Name: Mus musculus QVQLQQSGAELVRPGTSVKVSCKASGYAFSNHLIEWVKQRPGQGLEWIGVINPGSGGTNYIEKFKGKATLTADKSSSTAYMQLSSLTSDDSAVYFCARGANWDVGFAYWGQGTLVTVSA SEQ ID NO: 14 Sequence Name: Antibody GPN05-1 VH Sequence Type: DNA Organism Name: synthetic construct CAAGTGCAGCTGCAGCAATCTGGCGCCGAGCTGGTGAGACCTGGCACAAGCGTGAAGGTGAGCTGCAAGGCTAGCGGCTACGCCTTCAGCAACCACCTGATCGAGTGGGTGAAGCAGAGACCTGGCCAAGGCCTGGAGTGGATCGGCGTGATCAACCCTGGCAGCGGCGGCACCAACTACATCGAGAAGTTCAAGGGCAAGGCCACCCTGACCGCCGACAAGAGCAGCAGCACCGCCTACATGCAGCTGAGCAGCCTGACAAGCGACGACAGCGCCGTGTACTTCTGCGCTAGAGGCGCTAATTGGGACGTGGGGTTCGCGTATTGGGGCCAAGGCACCCTGGTGACCGTGAGCGCC SEQ ID NO: 15 Sequence Name: Antibody GPN05-1 VL Sequence Type: AA Organism Name: Mus musculus EIQMTQSPSSMSASLGDRITITCQATQDIVKNLNWYQQKPGKPPSFLIYYATELAEGVPSRFSGSGSGSDFSLTISNLESEDFADYYCLQFHEFPRTFGGGTKLEIK SEQ ID NO: 16 Sequence Name: Antibody GPN05-1 VL Sequence Type: DNA Organism Name: synthetic construct GAGATTCAGATGACACAGAGCCCTAGCAGCATGAGCGCTAGCCTGGGCGACAGAATCACCATCACCTGCCAAGCCACCCAAGACATCGTGAAGAACCTGAACTGGTATCAGCAGAAGCCTGGCAAGCCTCCTAGCTTCCTGATCTACTACGCCACCGAGCTGGCCGAGGGCGTGCCTAGCAGATTCAGCGGCAGCGGCAGCGGCAGCGACTTCAGCCTGACCATCAGCAACCTGGAGAGCGAGGACTTCGCCGACTACTACTGCCTGCAGTTCCACGAGTTCCCTAGAACCTTCGGCGGCGGCACCAAGCTGGAGATCAAG SEQ ID NO: 17 Sequence Name: Antibody GPN06-1 CDR-H1 Sequence Type: AA Organism Name: Mus musculus GYTFTDNW SEQ ID NO: 18 Sequence Name: Antibody GPN06-1 CDR-H1 Sequence Type: DNA Organism Name: synthetic construct GGCTACACCTTCACCGACAACTGG SEQ ID NO: 19 Sequence Name: Antibody GPN06-1 CDR-H2 Sequence Type: AA Organism Name: Mus musculus IDPSDSFT SEQ ID NO: 20 Sequence Name: Antibody GPN06-1 CDR-H2 Sequence Type: DNA Organism Name: synthetic construct ATCGACCCTAGCGACAGCTTCACC SEQ ID NO: 21 Sequence Name: Antibody GPN06-1 CDR-H3 Sequence Type: AA Organism Name: Mus musculus TRSGYYGSPKLGGDY SEQ ID NO: 22 Sequence Name: Antibody GPN06-1 CDR-H3 Sequence Type: DNA Organism Name: synthetic construct ACAAGAAGCGGCTACTATGGCTCCCCTAAATTGGGCGGCGACTAC SEQ ID NO: 23 Sequence Name: Antibody GPN06-1 CDR-L1 Sequence Type: AA Organism Name: Mus musculus SSISY SEQ ID NO: 24 Sequence Name: Antibody GPN06-1 CDR-L1 Sequence Type: DNA Organism Name: synthetic construct AGCAGCATCAGCTAC SEQ ID NO: 25 Sequence Name: Antibody GPN06-1 CDR-L2 Sequence Type: AA Organism Name: Mus musculus STS SEQ ID NO: 26 Sequence Name: Antibody GPN06-1 CDR-L2 Sequence Type: DNA Organism Name: synthetic construct AGCACAAGC SEQ ID NO: 27 Sequence Name: Antibody GPN06-1 CDR-L3 Sequence Type: AA Organism Name: Mus musculus HQWNSYPCT SEQ ID NO: 28 Sequence Name: Antibody GPN06-1 CDR-L3 Sequence Type: DNA Organism Name: synthetic construct CATCAGTGGAACAGCTACCCTTGCACC SEQ ID NO: 29 Sequence Name: Antibody GPN06-1 VH Sequence Type: AA Organism Name: Mus musculus QVQLQQPGAEIVRPGASVKLSCKASGYTFTDNWMGWVKQRPGQGLEWIGAIDPSDSFTNYNQNFKGKATLTVDTSSSTAYMQLSSLTSEDSAVYFCTRSGYYGSPKLGGDYWGQGTTLTVSS SEQ ID NO: 30 Sequence Name: Antibody GPN06-1 VH Sequence Type: DNA Organism Name: synthetic construct CAAGTGCAGCTGCAGCAGCCTGGCGCCGAGATCGTGAGACCTGGCGCTAGCGTGAAGCTGAGCTGCAAGGCTAGCGGCTACACCTTCACCGACAACTGGATGGGCTGGGTGAAGCAGAGACCTGGCCAAGGCCTGGAGTGGATCGGCGCCATCGACCCTAGCGACAGCTTCACCAACTACAATCAGAACTTCAAGGGCAAGGCGACGTTAACCGTCGACACAAGCAGCAGCACCGCCTACATGCAGCTGAGCAGCCTGACAAGCGAGGACAGCGCCGTGTACTTCTGCACAAGAAGCGGCTACTATGGCTCCCCTAAATTGGGCGGCGACTACTGGGGCCAAGGCACCACACTGACGGTTAGCTCC SEQ ID NO: 31 Sequence Name: Antibody GPN06-1 VL Sequence Type: AA Organism Name: Mus musculus QIVLTQSPAIMSASLGEEITLTCSASSSISYMHWYQQKSGTSPKLLIYSTSNLASGVPSRFSGSGSGTFYSLTISSVEAEDAADYYCHQWNSYPCTFGGGTKLEIK SEQ ID NO: 32 Sequence Name: Antibody GPN06-1 VL Sequence Type: DNA Organism Name: synthetic construct CAGATCGTGCTGACACAGAGCCCTGCCATCATGAGCGCTAGCCTGGGCGAGGAGATCACCCTGACCTGCAGCGCTAGCAGCAGCATCAGCTACATGCACTGGTATCAGCAGAAGAGCGGTACAAGCCCTAAGCTGCTGATCTACAGCACAAGCAACCTGGCTAGCGGCGTGCCTAGCAGATTCAGCGGCAGCGGCAGCGGCACCTTCTACAGCCTGACCATCAGCAGCGTGGAGGCCGAGGACGCCGCCGACTACTACTGCCATCAGTGGAACAGCTACCCTTGCACCTTCGGCGGCGGCACCAAGCTGGAGATCAAG SEQ ID NO: 33 Sequence Name: Antibody GPN07-1 CDR-H1 Sequence Type: AA Organism Name: Mus musculus GYTFTDYW SEQ ID NO: 34 Sequence Name: Antibody GPN07-1 CDR-H1 Sequence Type: DNA Organism Name: synthetic construct GGCTACACCTTCACCGACTACTGG SEQ ID NO: 35 Sequence Name: Antibody GPN07-1 CDR-H2 Sequence Type: AA Organism Name: Mus musculus IDPSDSYT SEQ ID NO: 36 Sequence Name: Antibody GPN07-1 CDR-H2 Sequence Type: DNA Organism Name: synthetic construct ATCGACCCTAGCGACAGCTACACC SEQ ID NO: 37 Sequence Name: Antibody GPN07-1 CDR-H3 Sequence Type: AA Organism Name: Mus musculus ARSGYYGSPKLGGDY SEQ ID NO: 38 Sequence Name: Antibody GPN07-1 CDR-H3 Sequence Type: DNA Organism Name: synthetic construct GCTAGAAGCGGCTACTATGGCTCCCCTAAATTGGGCGGCGACTAC SEQ ID NO: 39 Sequence Name: Antibody GPN07-1 CDR-L1 Sequence Type: AA Organism Name: Mus musculus SSISY SEQ ID NO: 40 Sequence Name: Antibody GPN07-1 CDR-L1 Sequence Type: DNA Organism Name: synthetic construct AGCAGCATCAGCTAC SEQ ID NO: 41 Sequence Name: Antibody GPN07-1 CDR-L2 Sequence Type: AA Organism Name: Mus musculus STS SEQ ID NO: 42 Sequence Name: Antibody GPN07-1 CDR-L2 Sequence Type: DNA Organism Name: synthetic construct AGCACAAGC SEQ ID NO: 43 Sequence Name: Antibody GPN07-1 CDR-L3 Sequence Type: AA Organism Name: Mus musculus HQWNSYPCT SEQ ID NO: 44 Sequence Name: Antibody GPN07-1 CDR-L3 Sequence Type: DNA Organism Name: synthetic construct CATCAGTGGAACAGCTACCCTTGCACC SEQ ID NO: 45 Sequence Name: Antibody GPN07-1 VH Sequence Type: AA Organism Name: Mus musculus QVQLQQPGAEIVRPGASVKLSCKASGYTFTDYWMNWVKQRPGQGLEWIGAIDPSDSYTNYNQEFNGKATLTVDTSSSTAYMQLSSLTSEDSAVYFCARSGYYGSPKLGGDYWGQGTTLTVSS SEQ ID NO: 46 Sequence Name: Antibody GPN07-1 VH Sequence Type: DNA Organism Name: synthetic construct CAAGTGCAGCTGCAGCAGCCTGGCGCCGAGATCGTGAGACCTGGCGCTAGCGTGAAGCTGAGCTGCAAGGCTAGCGGCTACACCTTCACCGACTACTGGATGAACTGGGTGAAGCAGAGACCTGGCCAAGGCCTGGAGTGGATCGGCGCCATCGACCCTAGCGACAGCTACACCAACTACAACCAAGAGTTCAACGGCAAGGCGACGTTAACCGTCGACACAAGCAGCAGCACCGCCTACATGCAGCTGAGCAGCCTGACAAGCGAGGACAGCGCCGTGTACTTCTGCGCTAGAAGCGGCTACTATGGCTCCCCTAAATTGGGCGGCGACTACTGGGGCCAAGGCACCACACTGACGGTTAGCTCC SEQ ID NO: 47 Sequence Name: Antibody GPN07-1 VL Sequence Type: AA Organism Name: Mus musculus QIVLTQSPAIMSASLGEEITLTCSASSSISYMHWYQQKSGTSPKLLIYSTSNLASGVPSRFSGSGSGTFYSLTISSVEAEDAADYYCHQWNSYPCTFGGGTKLEIK SEQ ID NO: 48 Sequence Name: Antibody GPN07-1 VL Sequence Type: DNA Organism Name: synthetic construct CAGATCGTGCTGACACAGAGCCCTGCCATCATGAGCGCTAGCCTGGGCGAGGAGATCACCCTGACCTGCAGCGCTAGCAGCAGCATCAGCTACATGCACTGGTATCAGCAGAAGAGCGGTACAAGCCCTAAGCTGCTGATCTACAGCACAAGCAACCTGGCTAGCGGCGTGCCTAGCAGATTCAGCGGCAGCGGCAGCGGCACCTTCTACAGCCTGACCATCAGCAGCGTGGAGGCCGAGGACGCCGCCGACTACTACTGCCATCAGTGGAACAGCTACCCTTGCACCTTCGGCGGCGGCACCAAGCTGGAGATCAAG SEQ ID NO: 49 Sequence Name: Antibody GPN11-10 CDR-H1 Sequence Type: AA Organism Name: Mus musculus GYTFTDCY SEQ ID NO: 50 Sequence Name: Antibody GPN11-10 CDR-H1 Sequence Type: DNA Organism Name: synthetic construct GGGTACACCTTTACCGACTGCTAC SEQ ID NO: 51 Sequence Name: Antibody GPN11-10 CDR-H2 Sequence Type: AA Organism Name: Mus musculus INPNSGYT SEQ ID NO: 52 Sequence Name: Antibody GPN11-10 CDR-H2 Sequence Type: DNA Organism Name: synthetic construct ATCAACCCCAACAGTGGCTACACG SEQ ID NO: 53 Sequence Name: Antibody GPN11-10 CDR-H3 Sequence Type: AA Organism Name: Mus musculus TRGDYYTSNLYDWFAY SEQ ID NO: 54 Sequence Name: Antibody GPN11-10 CDR-H3 Sequence Type: DNA Organism Name: synthetic construct ACAAGAGGCGATTACTACACCTCCAATCTCTATGACTGGTTTGCATAC SEQ ID NO: 55 Sequence Name: Antibody GPN11-10 CDR-L1 Sequence Type: AA Organism Name: Mus musculus QTVGTV SEQ ID NO: 56 Sequence Name: Antibody GPN11-10 CDR-L1 Sequence Type: DNA Organism Name: synthetic construct CAGACCGTAGGGACTGTG SEQ ID NO: 57 Sequence Name: Antibody GPN11-10 CDR-L2 Sequence Type: AA Organism Name: Mus musculus WAT SEQ ID NO: 58 Sequence Name: Antibody GPN11-10 CDR-L2 Sequence Type: DNA Organism Name: synthetic construct TGGGCAACG SEQ ID NO: 59 Sequence Name: Antibody GPN11-10 CDR-L3 Sequence Type: AA Organism Name: Mus musculus LQYGSVPPT SEQ ID NO: 60 Sequence Name: Antibody GPN11-10 CDR-L3 Sequence Type: DNA Organism Name: synthetic construct CTGCAGTATGGCAGCGTTCCACCCACC SEQ ID NO: 61 Sequence Name: Antibody GPN11-10 VH Sequence Type: AA Organism Name: Mus musculus QVNLLQSGAALVKPGASVRLSCKTSGYTFTDCYIHWVRQSHGKSLEWIGFINPNSGYTFYNEKFKSKATLTVAKSTNTAYMELSRLTSEDSATYFCTRGDYYTSNLYDWFAYWGQGTLVTVSS SEQ ID NO: 62 Sequence Name: Antibody GPN11-10 VH Sequence Type: DNA Organism Name: synthetic construct CAGGTCAATCTGCTGCAGTCCGGAGCTGCATTGGTCAAACCCGGAGCCAGCGTACGGCTTTCCTGTAAGACATCTGGGTACACCTTTACCGACTGCTACATTCACTGGGTAAGGCAGTCACATGGGAAGAGCCTTGAGTGGATTGGCTTCATCAACCCCAACAGTGGCTACACGTTCTACAACGAGAAGTTCAAGTCCAAAGCTACACTGACAGTGGCCAAAAGCACCAACACTGCCTATATGGAGCTGTCACGCTTGACATCCGAAGATAGTGCCACATATTTCTGCACAAGAGGCGATTACTACACCTCCAATCTCTATGACTGGTTTGCATACTGGGGTCAAGGCACCCTGGTTACCGTGTCATCT SEQ ID NO: 63 Sequence Name: Antibody GPN11-10 VL Sequence Type: AA Organism Name: Mus musculus DTVMTQSPASMSTSVGERVTVNCKASQTVGTVVAWFQQKPGQSPKRLIYWATNRHTGVPDRFTGSGFGRDFSLTISNVEAEDLAVYYCLQYGSVPPTFGGGTKLELK SEQ ID NO: 64 Sequence Name: Antibody GPN11-10 VL Sequence Type: DNA Organism Name: synthetic construct GACACAGTCATGACCCAATCACCAGCATCCATGAGCACTTCAGTTGGCGAGAGAGTGACCGTGAACTGTAAGGCCTCTCAGACCGTAGGGACTGTGGTTGCCTGGTTCCAGCAGAAACCAGGGCAAAGCCCCAAACGGCTGATATACTGGGCAACGAATCGACACACTGGTGTACCTGACCGCTTTACCGGCAGTGGGTTCGGAAGGGACTTCTCCCTCACCATTTCCAACGTCGAAGCCGAAGATCTTGCCGTGTACTATTGCCTGCAGTATGGCAGCGTTCCACCCACCTTTGGAGGAGGCACAAAGTTGGAGCTGAAG SEQ ID NO: 65 Sequence Name: Antibody GPN15-2 CDR-H1 Sequence Type: AA Organism Name: Mus musculus GYTFTNHN SEQ ID NO: 66 Sequence Name: Antibody GPN15-2 CDR-H1 Sequence Type: DNA Organism Name: synthetic construct GGCTACACATTTACCAATCACAAT SEQ ID NO: 67 Sequence Name: Anti...

Claims

1. An anti-gpNMB humanized antibody, a fragment thereof, or a derivative thereof, which specifically binds to at least one site in the region spanning from the PMEL Core Amyloid Fragment-like domain to the PKD domain of human gpNMB (glycoprotein nonmetastatic melanoma protein B).

2. The anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof described in claim 1, which specifically binds to a region including the amino acid residues D287 and / or H301 of human gpNMB having the amino acid sequence of SEQ ID NO:

209.

3. An anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to claim 1 or 2, which specifically binds to a region including the amino acid residues R214 and / or R215 of human gpNMB having the amino acid sequence of SEQ ID NO:

209.

4. An anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to claim 2 or 3, which specifically binds to one or more of the following regions of human gpNMB having the amino acid sequence of SEQ ID NO:209: a region containing amino acid residues K257 and / or D258, a region containing amino acid residues H268 and / or D269, a region containing amino acid residue K282, a region containing amino acid residue K316, a region containing amino acid residue K186, and a region containing amino acid residues H216 and / or R218.

5. The anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof described in any one of claims 1 to 4, wherein the anti-gpNMB antibody specifically binds to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of mouse gpNMB.

6. The anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 5, having one or more activities selected from the activity of reducing the number of dysfunctional microglia, the activity of removing amyloid β oligomers and / or phosphorylated tau and / or synuclein oligomers, the activity of increasing the number of synapses, and the activity of suppressing or restoring decline in cognitive function and / or motor function.

7. The anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 6, which is a monoclonal antibody or a fragment thereof or a derivative thereof.

8. A peptide comprising at least a heavy chain variable region, the heavy chain variable region being: (13) as CDR-H1, an amino acid sequence as set forth in SEQ ID NO:283, or an amino acid sequence in which one, two or three amino acid residues in the amino acid sequence as set forth in SEQ ID NO:283 have been substituted, deleted or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:283; as CDR-H2, an amino acid sequence as set forth in SEQ ID NO:285, or an amino acid sequence in which one, two or three amino acid residues in the amino acid sequence as set forth in SEQ ID NO:285 have been substituted, deleted or inserted, or an amino acid sequence having 62.5% or more, 75.0% or more, or 87.5% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:285; As CDR-H3, an amino acid sequence as set forth in SEQ ID NO:287, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence as set forth in SEQ ID NO:287 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:287, or (14) As CDR-H1, an amino acid sequence as set forth in SEQ ID NO:311, or an amino acid sequence in which any one, two, three, or four amino acid residues in the amino acid sequence as set forth in SEQ ID NO:311 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 70.0% or more, 80.0% or more, or 90.0% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:311, as CDR-H2, an amino acid sequence of SEQ ID NO:313, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence of SEQ ID NO:313 have been substituted, deleted, or inserted, or an amino acid sequence having 71.4% or more or 85.7% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO:313;(15) as CDR-H3, an amino acid sequence set forth in SEQ ID NO: 315, or an amino acid sequence in which any one, two, three, four, five, or six amino acid residues in the amino acid sequence set forth in SEQ ID NO: 315 have been substituted, deleted, or inserted, or an amino acid sequence having 60.0% or more, 66.6% or more, 73.3% or more, 80.0% or more, 86.6% or more, or 93.3% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 315; or (16) as CDR-grafting region-H1, an amino acid sequence set forth in SEQ ID NO: 271, or an amino acid sequence in which any one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 271 have been substituted, deleted, or inserted, except for tyrosine at position 27, asparagine at position 32, and tryptophan at position 33; As the CDR grafting region-H2, the amino acid sequence of SEQ ID NO:273, or the amino acid sequence of SEQ ID NO:273 in which any one, two, three, four, five, or six amino acid residues other than aspartic acid at position 55, phenylalanine at position 57, threonine at position 58, asparagine at position 59, tyrosine at position 60, and asparagine at position 61 have been substituted, deleted, or inserted; As the CDR grafting region-H3, the amino acid sequence of SEQ ID NO:275, or the amino acid sequence of SEQ ID NO:275 in which any one, two, three, four, five, or six amino acid residues other than arginine at position 98, glycine at position 100, and glycine at position 109 have been substituted, deleted, or inserted; (16) As the CDR grafting region-H1, an amino acid sequence set forth in SEQ ID NO: 299, or an amino acid sequence in which one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 299 have been substituted, deleted, or inserted;as CDR grafting region-H2, the amino acid sequence of SEQ ID NO:301, or an amino acid sequence in which, in the amino acid sequence of SEQ ID NO:301, any one, two, three, four, five, or six amino acid residues other than aspartic acid at position 52, tryptophan at position 54, aspartic acid at position 58, and proline at position 63 have been substituted, deleted, or inserted; as CDR grafting region-H3, the amino acid sequence of SEQ ID NO:303, or an amino acid sequence in which, in the amino acid sequence of SEQ ID NO:303, any one, two, three, four, five, or six amino acid residues other than arginine at position 99, threonine at position 100, tyrosine at position 102, tyrosine at position 105, tyrosine at position 107, and methionine at position 110 have been substituted, deleted, or inserted; The anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 7, comprising:

9. An anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 7, comprising at least a heavy chain variable region, the heavy chain variable region having: (1) an amino acid sequence set forth in SEQ ID NO: 295 or an amino acid sequence having 60% or more homology with the amino acid sequence set forth in SEQ ID NO: 295; or (2) an amino acid sequence set forth in SEQ ID NO: 323 or an amino acid sequence having 60% or more homology with the amino acid sequence set forth in SEQ ID NO:

323.

10. An anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to claim 8 or 9, wherein the heavy chain variable region comprises as a framework sequence a framework sequence of any class of human immunoglobulin.

11. The anti-gpNMB humanized antibody or its fragment or derivative thereof according to any one of claims 8 to 10, further comprising a heavy chain constant region, said heavy chain constant region having an amino acid sequence of a heavy chain constant region of any class of human immunoglobulin.

12. A nucleic acid sequence comprising at least a light chain variable region, the light chain variable region being: (13) as CDR-L1, an amino acid sequence as set forth in SEQ ID NO:289, or an amino acid sequence in which one or two amino acid residues in the amino acid sequence as set forth in SEQ ID NO:289 have been substituted, deleted or inserted, or an amino acid sequence having 60.0% or more or 80.0% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:289; as CDR-L2, an amino acid sequence as set forth in SEQ ID NO:291, or an amino acid sequence in which one amino acid residue in the amino acid sequence as set forth in SEQ ID NO:291 has been substituted, deleted or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:291; and (13) as CDR-L3, an amino acid sequence as set forth in SEQ ID NO:293, or an amino acid sequence in which any one, two, or three amino acid residues in the amino acid sequence as set forth in SEQ ID NO:293 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:293; or (14) as CDR-L1, an amino acid sequence as set forth in SEQ ID NO:317, or an amino acid sequence in which any one, two, three, or four amino acid residues in the amino acid sequence as set forth in SEQ ID NO:317 have been substituted, deleted, or inserted, or an amino acid sequence having 63.6% or more, 72.7% or more, 81.8% or more, or 90.9% or more homology (preferably identity) with the amino acid sequence as set forth in SEQ ID NO:317; As CDR-L2, an amino acid sequence of SEQ ID NO: 319, or an amino acid sequence in which any one amino acid residue in the amino acid sequence of SEQ ID NO: 319 has been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more homology (preferably identity) with the amino acid sequence of SEQ ID NO: 319, and(15) as CDR-L3, an amino acid sequence set forth in SEQ ID NO: 321, or an amino acid sequence in which any one, two, or three amino acid residues in the amino acid sequence set forth in SEQ ID NO: 321 have been substituted, deleted, or inserted, or an amino acid sequence having 66.6% or more, 77.7% or more, or 88.8% or more homology (preferably identity) with the amino acid sequence set forth in SEQ ID NO: 321; or (16) as CDR-grafting region-L1, an amino acid sequence set forth in SEQ ID NO: 277, or an amino acid sequence in which any one, two, three, or four amino acid residues in the amino acid sequence set forth in SEQ ID NO: 277 have been substituted, deleted, or inserted, other than isoleucine at position 29, tyrosine at position 31, and histidine at position 33; as CDR grafting region-L2, an amino acid sequence as set forth in SEQ ID NO:279, or an amino acid sequence in which one or two amino acid residues other than threonine at position 50 in the amino acid sequence as set forth in SEQ ID NO:279 have been substituted, deleted, or inserted; as CDR grafting region-L3, an amino acid sequence as set forth in SEQ ID NO:281, or an amino acid sequence in which one, two, or three amino acid residues other than histidine at position 88, glutamine at position 89, tryptophan at position 90, serine at position 92, tyrosine at position 93, proline at position 94, and cysteine ​​at position 95 in the amino acid sequence as set forth in SEQ ID NO:281 have been substituted, deleted, or inserted; (16) As the CDR grafting region-L1, the amino acid sequence of SEQ ID NO: 305, or the amino acid sequence of SEQ ID NO: 305 in which any one, two, three, four, five, or six amino acid residues other than leucine at position 31, tyrosine at position 37, and glutamic acid at position 39 have been substituted, deleted, or inserted; As the CDR grafting region-L2, the amino acid sequence of SEQ ID NO: 307, or the amino acid sequence of SEQ ID NO: 307 in which any one or two amino acid residues other than lysine at position 55 have been substituted, deleted, or inserted;The anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 11, having, as a CDR grafting region-L3, an amino acid sequence set forth in SEQ ID NO: 309, or an amino acid sequence in which any one, two, or three amino acid residues other than phenylalanine at position 94 of the amino acid sequence set forth in SEQ ID NO: 309 have been substituted, deleted, or inserted.

13. An anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 11, comprising at least a light chain variable region, the light chain variable region having: (1) an amino acid sequence set forth in SEQ ID NO:297 or an amino acid sequence having 60% or more identity with the amino acid sequence set forth in SEQ ID NO:297; or (2) an amino acid sequence set forth in SEQ ID NO:325 or an amino acid sequence having 60% or more identity with the amino acid sequence set forth in SEQ ID NO:

325.

14. The anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to claim 12 or 13, wherein the light chain variable region comprises as a framework sequence a framework sequence of any class of human immunoglobulin.

15. The anti-gpNMB humanized antibody or its fragment or derivative thereof according to any one of claims 12 to 14, further comprising a light chain constant region, said light chain constant region having an amino acid sequence of a light chain constant region of any class of human immunoglobulin.

16. The anti-gpNMB humanized antibody or its fragment or derivative thereof according to any one of claims 1 to 15, which is a Fab, scFv, diabody, nanobody, VHH, bispecific antibody, or multispecific antibody, or a derivative thereof.

17. An anti-gpNMB humanized antibody, or a fragment thereof, or a derivative thereof, which competitively binds to at least one site in the region spanning from the PMEL-CAF-like domain to the PKD domain of gpNMB with the anti-gpNMB antibody, or a fragment thereof, or a derivative thereof described in any one of claims 1 to 16.

18. A nucleic acid molecule consisting of a polynucleotide sequence encoding the anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 17.

19. A cloning or expression vector comprising at least one nucleic acid molecule according to claim 18.

20. A recombinant cell into which the vector according to claim 19 has been introduced.

21. A method for producing an anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 17, comprising culturing a recombinant cell according to claim 20.

22. A method for producing the anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof according to any one of claims 1 to 17, comprising administering to an animal a polypeptide having an amino acid sequence identical to one or more regions selected from the following of human gpNMB having the amino acid sequence of SEQ ID NO:209: a region comprising amino acid residues D287 and / or H301, a region comprising amino acid residues R214 and / or R215, a region comprising amino acid residues K257 and / or D258, a region comprising amino acid residues H268 and / or D269, a region comprising amino acid residue K282, a region comprising amino acid residue K316, a region comprising amino acid residue K186, and a region comprising amino acid residues H216 and / or R218, and collecting the antibody or a fragment thereof or a derivative thereof produced in the animal's body.

23. A vaccine having activity of promoting the production of an anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof described in any one of claims 1 to 17, comprising a polypeptide having an amino acid sequence identical to a region including amino acid residues D287 and / or H301 of human gpNMB having the amino acid sequence of SEQ ID NO: 209, and / or a region including amino acid residues R214 and / or R215.

24. A pharmaceutical composition comprising as an active ingredient one or more selected from the group consisting of the anti-gpNMB humanized antibody or a fragment thereof or a derivative thereof described in any one of claims 1 to 17, the nucleic acid molecule described in claim 18, the vector described in claim 19, and the recombinant cell described in claim 20.

25. The pharmaceutical composition of claim 24, for one or more uses selected from: reducing the number of dysfunctional microglia in a subject; removing amyloid beta oligomers in a subject; increasing the number of synapses in a subject; removing phosphorylated tau and / or inhibiting tau accumulation in a subject; removing synuclein and / or synuclein aggregates in a subject; inhibiting or reversing a decline in cognitive function in a subject; inhibiting or reversing a decline in motor function in a subject; and treating or preventing a neurodegenerative disease in a subject.

26. A pharmaceutical composition comprising as an active ingredient an agent having activity to reduce the number of dysfunctional microglia, for one or more uses selected from the following: removal of amyloid beta oligomers in a subject; increasing the number of synapses in a subject; removal of phosphorylated tau and / or inhibition of tau accumulation in a subject; removal of synuclein and / or synuclein aggregates in a subject; inhibiting or restoring a decline in cognitive function in a subject; inhibiting or restoring a decline in motor function in a subject; and treating or preventing a neurodegenerative disease in a subject.

27. The pharmaceutical composition of claim 24 for treating or preventing a neurodegenerative disease in a subject.

28. The pharmaceutical composition according to any one of claims 25 to 27, wherein the neurodegenerative disease is a disease caused by accumulation of one or more proteins selected from amyloid beta, tau, synuclein, polyglutamine, RNA translation-derived protein, and prion.

29. Neurodegenerative diseases include Alzheimer's disease, Frontotemporal Lobar Degeneration (FTLD-Tau), Frontotemporal Dementia (FTD), Primary Age-Related Tauopathy (PART), Chronic Traumatic Encephalopathy (CTE), Pick's Disease, Corticobasal Degeneration (CBD or CBS), Progressive Supranuclear Palsy (PSP), Globuloglial Tauopathy (GGT), Argyrophilic Grain Dementia (AGD) (Argyrophilic Grain Disease), Age-Related Tauastrogliotauopathy (ARTAG), Familial British Dementia (FBA) BD), familial Danish dementia (FDD), FTDP17, multisystem tauopathy with dementia (MSTD), neurofibrillary tangle dementia, diffuse neurofibrillary tangle disease with calcification (DNTC), white matter tauopathy with globular glial inclusions (WMT-GGI), Parkinson's disease, Huntington's disease, spinocerebellar degeneration, hereditary spinocerebellar ataxia, spinal-bulbar muscular atrophy, dementia with Lewy bodies, Creutzfeldt-Jakob disease (CJD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD-TDP, FTLD-FUS), and repeat disease. The pharmaceutical composition according to any one of claims 25 to 27, which is one or more diseases selected from the group consisting of FTLD-TDP, FTLD-FUS, and repeat disease.

30. The pharmaceutical composition of claim 29, wherein the neurodegenerative disease is Alzheimer's disease.

31. The pharmaceutical composition of claim 29, wherein the neurodegenerative disease is Parkinson's disease, dementia with Lewy bodies, multiple system atrophy (MSA), or amyotrophic lateral sclerosis (ALS).

32. The pharmaceutical composition of claim 30 or 31, further comprising a second active ingredient.

33. The pharmaceutical composition according to claim 32, wherein the second active ingredient is one or more selected from the group consisting of an anti-Tau antibody, an anti-amyloid beta antibody, an anti-CD33 antibody, an anti-semaphorin 4D antibody, an anti-TNFα antibody, an anti-sortilin antibody, an anti-galactose-specific lectin (galectin) 3 antibody, an anti-TREM2 (Triggering receptor expressed on myeloid cells 2) antibody, an anti-IL-1β antibody, an anti-CD38 antibody, an anti-MS4A antibody, and an anti-synuclein antibody.

34. The pharmaceutical composition of claim 32, wherein the second active ingredient is a vaccine comprising a full-length or partial-length polypeptide of one or more proteins selected from Tau, amyloid beta, CD33, semaphorin 4D, TNFα, sortilin, galactose-specific lectin (galectin) 3, and TREM2 (Triggering receptor expressed on myeloid cells 2), or a nucleic acid encoding the same.

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