Insulin amyloid polymerized protein, antibody, antibody-producing b cells, and medical composition

Abstract

To provide an insulin amyloid polymerized protein, an antibody, antibody-producing B cells and a medical composition capable of effectively preventing and treating Alzheimer type dementia with little side effects. An insulin amyloid polymerized protein is collected from a patient with Alzheimer type dementia to which insulin has been administered for use in the treatment of the patient. An insulin amyloid polymerized protein composition for use in the treatment of a patient with Alzheimer type dementia, wherein an insulin amyloid polymerized protein is obtained by chemically bonding insulin and amyloid. Also provided are an antibody therefor, antibody-producing B cells, and a medical composition.

Description

Insulin amyloidogenic polymerized protein, antibody, antibody-producing B cells, and medical composition

[0001] The present invention relates to proteins, antibodies, antibody-producing B cells, and medical compositions containing them that can be used to treat or prevent dementia patients, particularly Alzheimer's disease. This application claims priority based on U.S. provisional patent application No. 2024-003488, filed January 12, 2024, the contents of which are incorporated herein by reference.

[0002] In recent years, the aging society has been increasing, and a wide range of issues are piling up. Among these, dementia, which is accompanied by a breakdown in personality and mind beyond the decline in physical function, causes unbearable pain for the patient, their family, and caregivers. Coupled with the high rate of coexistence with other diseases such as diabetes, which are increasing in the aging population, there is a strong demand for treatment methods.

[0003] Among dementia types, Alzheimer's disease (AD) accounts for 60-70% of dementia patients, and the number of patients is rapidly increasing worldwide. According to Alzheimer's Disease International, the number of patients is estimated to be 50 million at present, and is expected to increase to 150 million by 2050. There are said to be 5-6 million patients in Japan, and there is a strong demand worldwide for treatment and prevention methods.

[0004] Conventional treatments for Alzheimer's disease, such as Aricept (which increases the amount of acetylcholine in the brain by inhibiting the enzyme acetylcholine degrading, activating the cholinergic nervous system in the brain and slowing the progression of cognitive decline), can alleviate symptoms but cannot halt the progression of the disease, and more effective treatments are therefore needed.

[0005] Patent Literature 1 discloses a method for treating and preventing Alzheimer's disease, which comprises administering a composition containing a therapeutically effective amount of an anti-amyloid β (Aβ) protofibril antibody. This technology, based on the amyloid hypothesis that amyloid β peptide plays a central role in the pathogenesis of Alzheimer's disease, aims to prevent and / or delay the onset of AD in early-stage AD subjects by reducing the brain amyloid level in amyloid-positive AD subjects.

[0006] Special table 2021-532126 publication

[0007] The use of anti-amyloid β antibodies such as those described in Patent Document 1 is said to be effective in removing amyloid β that accumulates in the brains of Alzheimer's disease patients, and in clinical trials has been shown to slow the rate of deterioration of cognitive function. However, in the opinion of the present inventors, amyloid proteins themselves are highly toxic, and artificial antibodies against them, although clinically effective, are of concern as having strong side effects.

[0008] Based on findings on amyloid, research is being conducted into therapies using substances that exhibit immune effects against dementia and Alzheimer's disease, but no improvements in the disease have yet been reported. The reasons for this are: 1) active immunization is primarily focused on specific epitopes, such as amyloid Aβ42, and the vaccination period is short; 2) passive immunization has primarily focused on monoclonal antibodies against the N-terminus of amyloid protein, amyloid Aβ mid-domain, and soluble amyloid Aβ, but the effectiveness has varied, ranging from ineffective to severe side effects. For these reasons, analysis leading to treatments has traditionally been difficult.

[0009] The present inventors have been investigating a more effective treatment method for Alzheimer's disease with fewer side effects, while focusing on the relationship between Alzheimer's disease and amyloid. They have therefore focused on the relationship between insulin use and Alzheimer's disease in diabetic patients.

[0010] It is widely known that diabetes patients generally have a high prevalence of dementia due to years of hyperglycemic stress and the progression of arteriosclerosis. The proportion of elderly people with diabetes and the proportion of elderly people with dementia are increasing significantly along with the elderly population, just like the Japanese population distribution. Diabetes is associated with three major complications (eye, kidney, and nerve), with dementia being called the fourth complication. It is estimated that the number of dementia patients in Japan will reach 7 million in five years, meaning that one in five people over the age of 65 will have dementia.

[0011] Clinical epidemiology has also proven that diabetes poses a high risk for dementia and Alzheimer's disease, but there are exceptions to this association. In the Vienna Trans Danube Aging Study (VITA study), among patients with the highest plasma Aβ42 levels and the highest risk of Alzheimer's disease, those who used insulin as a treatment for diabetes were most likely to maintain normal cognitive function. In other words, despite the high systemic risk of Alzheimer's disease in diabetic patients, it has been concluded that insulin use may have some protective factor. Many diabetic patients are forced to receive subcutaneous insulin injections as the disease progresses, but it is known that patients who have already been using insulin for a long time rarely experience cognitive decline in the elderly. Furthermore, animal experiments have shown that connective tissue pseudotumors, or insulin balls, form subcutaneously in long-term insulin users, and amyloid polymerized protein (amyloid fibrils) are identified in these insulin ball pseudotumors.

[0012] Given these circumstances, it was anticipated that elucidating the relationship between insulin administration and amyloid associated with Alzheimer's disease, as well as the behavior of these molecules in humans, particularly the properties of subcutaneously injected insulin, would provide significant insight into methods for treating Alzheimer's disease. However, because there was no technology to quantify the properties of insulin in subcutaneous tissue in humans, it was difficult to clarify these properties and consider methods for applying them to treatment.

[0013] The present invention has been made in consideration of the above circumstances, and its object is to provide an insulin amyloid-polymerized protein, an antibody, an antibody-producing B cell, and a medical composition that can effectively treat and prevent Alzheimer's dementia with few side effects.

[0014] In order to solve the above problems, the present invention has the following aspects. [1] An insulin amyloid-polymerized protein collected from a patient to whom insulin has been administered, for use in treating a patient with Alzheimer's dementia. [2] The insulin amyloid-polymerized protein according to [1], which is collected from the patient using three-dimensional information on the patient's subcutaneous tissue. [3] An insulin amyloid-polymerized protein composition for use in treating a patient with Alzheimer's dementia, which is obtained by chemically bonding insulin and amyloid. [4] The insulin amyloid-polymerized protein according to [1] to [3], which cross-reacts with both anti-insulin antibodies and anti-amyloid antibodies. [5] An antibody that cross-reacts with the insulin amyloid-polymerized protein according to [1] to [3]. [6] The antibody according to [5], collected from the serum of a patient with insulin amyloid-polymerized protein. [7] Antibody-producing B cells that produce the antibody according to [5]. [8] A medical composition for use in treating patients with Alzheimer's disease, comprising the insulin amyloid-polymerized protein described in [1] or [3], or the antibody described in [5].

[0015] According to the present invention, it is possible to provide an insulin amyloid-polymerized protein, an antibody, an antibody-producing B cell, and a medical composition that can effectively treat and prevent Alzheimer's dementia with few side effects.

[0016] 1 is a schematic diagram of the creation of a subcutaneous three-dimensional map in an example. 2 is a three-dimensional map showing the distribution of insulin amyloid-polymerized protein obtained from VTTQ information for a portion of abdominal wall subcutaneous tissue. 3 is a graph showing the ELISA standard curve used in Test Example 3 of this example. 4 is a graph showing the results of a comparison of the evaluation of human plasma anti-amyloid β1-42 antibodies.

[0017] The insulin amyloidogenic polymerized protein, antibody, antibody-producing B cells, and medical composition according to the present invention will be described below with reference to exemplary embodiments, although the present invention is not limited to the following exemplary embodiments.

[0018] [Insulin amyloid-forming polymerized protein] (Insulin amyloid-forming polymerized protein collected from a patient with Alzheimer's disease) The insulin amyloid-forming polymerized protein of this embodiment is used for treating a patient with Alzheimer's disease. Furthermore, the insulin amyloid-forming polymerized protein of this embodiment is collected from the patient to whom insulin has been administered.

[0019] Patients with Alzheimer's dementia primarily include those who can confirm any of the various symptoms of Alzheimer's dementia. They also include patients who do not currently have significant symptoms of Alzheimer's dementia but are likely to develop Alzheimer's dementia and are eligible for preventive treatment, as described below, and patients who have previously developed Alzheimer's dementia and are eligible for treatment to prevent recurrence. Patients with Alzheimer's dementia are primarily humans, but veterinary treatment can also be applied to other animals. Examples of animals include mammals. Treatment for patients with Alzheimer's dementia broadly includes goals such as cure, prevention, and recurrence prevention.

[0020] The insulin amyloid-forming polymerized protein is a protein in which insulin and amyloid are bound together. The insulin amyloid-forming polymerized protein may also be a multimeric protein consisting of multiple insulins and / or multiple amyloids. In particular, the insulin amyloid-forming polymerized protein may form a fibrous tissue, such as that found in connective tissue.

[0021] The insulin amyloid-polymerized protein is preferably collected from a patient with Alzheimer's disease using three-dimensional subcutaneous information from the patient. Here, the three-dimensional subcutaneous information may be obtained by any means capable of acquiring information on the three-dimensional distribution of a specific component within the skin. Examples of means for acquiring the three-dimensional subcutaneous information include acoustic radiation force impulse (ARFI), which measures tissue displacement using microacoustic pressure ultrasound.

[0022] More specifically, the insulin amyloid-forming polymerized protein is preferably obtained from connective tissue pseudotumors (insulin balls) formed subcutaneously in patients administered insulin, primarily by subcutaneous injection. For example, it is also preferable to obtain the insulin amyloid-forming polymerized protein by analyzing information on the distribution of the insulin amyloid-forming polymerized protein in the insulin balls from the three-dimensional subcutaneous information.

[0023] The inventors hypothesized that intracerebral amyloid accumulation is important in the pathogenesis of Alzheimer's disease, and that long-term subcutaneous insulin administration may have some protective effect on the mechanism of intracerebral amyloid deposition, thereby suppressing the progression of dementia. They focused on insulin amyloid-producing polymerized proteins, which are thought to be present in subcutaneous pseudotumors (insulin balls) in patients undergoing insulin therapy. However, because there was no technology available to quantify the characteristics of insulin-producing subcutaneous tissue in humans, it was impossible to examine the extent and progression of these pseudotumors in the subcutaneous tissue, the insulin and amyloid in the surrounding area, and the immune and other responses to them. To study these issues, it was necessary to visualize the specific location and amount of insulin amyloid-producing polymerized proteins present in the subcutaneous tissue.

[0024] The present inventors focused on ARFI, which uses a special micro-ultrasound technology to detect fluctuations in acoustic pressure. This technology uses acoustic pressure to induce minute displacements in soft tissue, and then measures the displacement using ultrasound to quantify the tissue stiffness. This technique allows for virtual touch tissue quantification (VTTQ), which measures the stiffness of deep tissues as if touching them directly. The inventors used VTTQ to virtually sense the stiffness of subcutaneous tissue, created a 3D map of the subcutaneous tissue from the quantitative stiffness values, evaluated the subcutaneous immune phenomenon of insulin amyloid-polymerized protein (AAP) at different stiffness levels, and confirmed the simultaneous presence of insulin-induced amyloid polymerization and insulin. This allowed for histological evaluation of immune cells around the same site, providing information on the formation of insulin amyloid-polymerized protein (AAP) and its subcutaneous distribution in insulin-administered subjects.

[0025] They then discovered an insulin amyloid-forming polymerized protein that can be obtained from an insulin recipient, and that can be further administered to the recipient to produce antibodies, or by administering antibodies, which they believe will have an effect on the amyloid that accumulates in the brains of Alzheimer's disease patients, without causing side effects.

[0026] The insulin amyloidogenic polymerized protein is preferably a protein that cross-reacts with both anti-insulin antibodies and anti-amyloid antibodies. The cross-reaction of the insulin amyloidogenic polymerized protein with both anti-insulin antibodies and anti-amyloid antibodies can be confirmed using any immunochemical method. For example, in vitro Western blotting or ELISA, or in vivo immunostaining, can be used. In this embodiment, the protein is preferably one whose cross-reaction can be confirmed by immunostaining of tissue.

[0027] (Synthetic Amyloidogenic Insulin Polymerized Protein) The insulin amyloidogenic polymerized protein of this embodiment may also be the insulin amyloidogenic polymerized protein composition for use in treating patients with Alzheimer's disease, which is obtained by chemically bonding insulin and amyloid. Here, the insulin may be primarily exogenously administered insulin.

[0028] The insulin amyloidogenic polymerization protein of this embodiment may also be an insulin amyloidogenic polymerization protein that cross-reacts with both the anti-insulin antibody and the anti-amyloid antibody.

[0029] [Antibody] The antibody of this embodiment is an anti-insulin amyloidotic polymerization protein antibody that cross-reacts with insulin amyloidotic polymerization protein.

[0030] The antibody of this embodiment is preferably an antibody collected from the serum of a patient with insulin amyloidogenic polymerized protein. That is, since antibodies against insulin amyloidogenic polymerized protein are produced in patients with insulin amyloidogenic polymerized protein, the antibody can be collected from the serum of the patient. The antibody collected from serum may be in a form that is contained in the serum as is, or may be purified from the serum. As for the form of the antibody, conventionally known antibodies that can be collected from serum and those that have undergone a purification process can be used.

[0031] In another embodiment, the antibody may be a polyclonal antibody or a monoclonal antibody. In the case of a polyclonal antibody, it can be produced using the insulin amyloid-polymerized protein as an antigen, as described below. In the case of a monoclonal antibody, a conventionally known method for producing an antibody that specifically binds to the insulin amyloid-polymerized protein can be used as appropriate.

[0032] Polyclonal antibodies can also be produced by collecting antibodies from other animals, generally by administering the insulin amyloidogenic polymerized protein as an immunogen to an animal capable of producing antibodies, collecting serum from the animal, and purifying the antibodies from the serum.

[0033] [Antibody-Producing B Cells] The antibody-producing B cells of this embodiment are antibody-producing B cells that produce antibodies that specifically bind to the aforementioned insulin amyloidogenic polymerized protein.

[0034] The antibody-producing B cells may be collected from a patient having the insulin amyloidogenic polymerized protein or the antibody. Furthermore, the antibody-producing B cells may be produced using other cells in addition to the collected cells. The produced antibody-producing B cells may have the antibody gene locus or a part thereof inserted or substituted into the antibody gene locus. The other cells may be human or non-human. Alternatively, the antibody-producing B cells may be obtained by any known means for obtaining antibody-producing B cells.

[0035] [Medical Composition] The medical composition of this embodiment is a medical composition for use in treating patients with Alzheimer's disease, and is a medical composition containing the insulin amyloid-polymerized protein or the antibody described above.

[0036] The medical composition may contain, in addition to the above-mentioned protein or antibody, other medically or pharmaceutically acceptable components. For example, depending on the type and form of the drug to be administered, the medical composition may contain components appropriate for those types and forms.

[0037] The medical composition of this embodiment can be used to treat diseases associated with Alzheimer's disease or diseases with similar mechanisms. For example, it can be used to treat amyloid-related diseases. Here, "treatment" broadly includes medical treatment of diseases, such as symptom improvement, prevention, and prognosis treatment.

[0038] The form of the medical composition of this embodiment is not particularly limited and can be, for example, a solution, a dispersion such as a sol or gel, or a powder. The medical composition can be administered orally in the form of, for example, a tablet, capsule, or elixir, or parenterally in the form of an enema. Pharmaceutically acceptable carriers include those typically used in the formulation of pharmaceuticals containing medical compositions, without particular limitation. More specific examples include binders, excipients, bulking agents, and solvents. The medical composition of this embodiment may contain additives. Examples of additives include lubricants, sweeteners, flavoring agents, stabilizers, pH buffers, solubilizers, antioxidants, and preservatives.

[0039] The medical composition of this embodiment can be formulated by appropriately combining the above-mentioned components and mixing them in a unit dosage form required for generally accepted pharmaceutical practice.

[0040] When the medical composition of this embodiment is administered with insulin amyloid-polymerized protein, it induces the production of antibodies in the patient, thereby exerting a vaccine-like action and effect in the sense that it utilizes the immune action against the antigen. When the antibody is administered, it can be used as an antibody drug.

[0041] (Effects of this embodiment) According to this embodiment, it is possible to provide an insulin amyloid-polymerized protein, an antibody, an antibody-producing B cell, and a medical composition that can effectively treat and prevent Alzheimer's dementia with few side effects.

[0042] Conventional therapeutic methods using anti-amyloid antibodies have the potential for severe side effects due to the toxicity of amyloid proteins themselves. In the present invention, subcutaneous 3D information on the formation and distribution of insulin amyloid-forming polymerized proteins in patients administered insulin was obtained. This information made it possible to extract insulin amyloid-forming polymerized proteins from the patients themselves, and to obtain antibodies and antibody-producing cells against insulin amyloid-forming polymerized proteins, as well as therapeutic drugs using these.

[0043] The insulin amyloid-forming polymerized protein and its antibody are expected to suppress Alzheimer's disease, similar to the case of diabetes patients administered insulin. Furthermore, since the insulin amyloid-forming polymerized protein of this embodiment is collected from the patient himself, it is thought that it will be able to suppress Alzheimer's disease without side effects, similar to the case of diabetes patients administered insulin.

[0044] Furthermore, administration of insulin amyloid-polymerized protein to patients is thought to produce antibodies against insulin amyloid-polymerized protein and exert an inhibitory effect on amyloid proteins involved in Alzheimer's dementia. In other words, administration of insulin amyloid-polymerized protein is thought to have an immunological preventive and inhibitory effect against Alzheimer's dementia, a so-called vaccine-like effect. No immunological means of preventing Alzheimer's dementia have been reported to date.

[0045] (Other Aspects of This Embodiment) This embodiment also includes the following other aspects. Another aspect of this embodiment is a method for producing a therapeutic drug for Alzheimer's disease, using the insulin amyloidotic polymerization protein, antibody, antibody-producing B cells, or medical composition. Another aspect of this embodiment is use of the insulin amyloidotic polymerization protein, antibody, antibody-producing B cells, or medical composition for producing a therapeutic drug for Alzheimer's disease. Another aspect of this embodiment is use of the insulin amyloidotic polymerization protein, antibody, antibody-producing B cells, or medical composition for treating Alzheimer's disease. Another aspect of this embodiment is use of the insulin amyloidotic polymerization protein, antibody, antibody-producing B cells, or medical composition for use in Alzheimer's disease. Another aspect of this embodiment is a method for treating Alzheimer's disease, using the insulin amyloidotic polymerization protein, antibody, antibody-producing B cells, or medical composition.

[0046] Although the embodiment of the present invention has been described above, the present invention is not limited to the above embodiment and various modifications can be made.

[0047] The effects of the present invention will be made clearer by the following examples and comparative examples. Note that the present invention is not limited to the following examples, and can be practiced by making appropriate changes within the scope of the present invention.

[0048] (Test Example 1: VTTQ Test) Eight patients receiving insulin underwent microacoustic pressure ultrasound examination of the abdominal wall subcutaneous tissue, and the hardness and extent of the tumor site were measured using VTTQ.

[0049] The test was carried out as follows: 1. Subcutaneous 3D Mapping Figure 1 is a schematic diagram of the subcutaneous 3D mapping process. As shown in (a), microacoustic pressure ultrasound testing, described below, was performed on areas 1 to 9 of the subject's abdomen. The special ultrasound (microacoustic pressure ultrasound testing) that we focused on this time can measure the hardness of living tissue, so we used this numerical data as a virtual tactile sensation to measure the subcutaneous hardness of each area, and created a subcutaneous 3D map, as shown in (b).

[0050] 2. Test measurement conditions: To confirm the immune response to insulin-amyloid polymerization protein systemically, specific antibodies to various amyloid polymerization proteins were evaluated at the site of long-term subcutaneous insulin administration. Specific antibodies to various amyloid proteins (Aβ40, Aβ42, etc.) and polymerized Aβ1-42 human amyloid protein were confirmed. Cognitive function was assessed using a cognitive function assessment battery (Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR)), and the correlation was confirmed.

[0051] Microacoustic pressure ultrasound was measured using an Acuson S3000™ and a 9L4 probe (6.5 MHz ± 20%) (Siemens Medical Solutions, Mountain View, CA, USA). A 0.5 cm-thick spacer (Yasojima Proceed Co., Ltd., Osaka, Japan) was used between the skin and the transducer to minimize errors in the microacoustic pressure. The hardness and extent of the tumor site were measured using a VTTQ. The subject's control site (back and lumbar region) was measured as an internal standard. The tumor site was identified as a site with a microacoustic pressure value 50% or higher than the control site (back and lumbar region). The subject's control site (flank or back and lumbar region) was measured as an internal standard. A "3D map" was created from the digitized data.

[0052] Figure 2 is a three-dimensional map showing the distribution of insulin amyloid-polymerized protein (AMP) in a portion of abdominal wall subcutaneous tissue obtained from VTTQ information. Microacoustic pressure ultrasound examination color-coded tissue regions according to their hardness, with lighter colors indicating areas of high hardness. As shown in the figure, deep within area A (the epidermis is shown in light color) with high hardness in the epidermis of the abdominal wall subcutaneous tissue, there is area B, surrounded by a light color. That is, although it has previously been determined that area A is a pseudotumor upon contact with the skin surface, there has been no means of specifically analyzing how insulin balls are distributed under the skin. Area B in the figure is a high-grade tumor area where insulin has accumulated and formed insulin balls, and insulin amyloid-polymerized protein is present deep in the subcutaneous tissue.

[0053] This study provided information on the three-dimensional distribution of insulin amyloid-polymerized proteins in patients who received insulin. This information may be useful for treating Alzheimer's disease by extracting insulin amyloid-polymerized proteins or their antibodies from the patients themselves.

[0054] (Test Example 2: Immunostaining Evaluation) Eight patients who received insulin were subcutaneously injected with 0.1 units / standard body weight (kg) of insulin aspart. Thereafter, serum insulin aspart was measured under serum conditions every 30 minutes until 240 minutes. For the ELISA method, Serum iso-insulin (Mercodia AB, Uppsala, Sweden) and human insulin (Roche Diagnostics, Tokyo, Japan) were used. As a result, it was confirmed that human amyloid protein-specific antibodies were present in the serum of all eight patients. The antibody used was Human anti-Aβ42 antibody (CD Creative Diagnostics, USA). This antibody may have systemic immune effects.

[0055] Immunostaining was performed on insulin amyloid-polymerized protein sites in the high-grade tumor sites from fine needle biopsies. Specifically, the simultaneous presence of insulin-induced amyloid polymerization (Congo red and Thioflavin-S were obtained from Sigma-Aldrich (St. Louis, MO, USA)) and insulin was confirmed. Histological evaluation of immune system cells around the site was also performed. A fluorescence microscope was used to irradiate excitation wavelengths and read and measure specific wavelength laser light sources (wavelength of 450 nm, and an emission wavelength of 490 nm). The results confirmed the simultaneous presence of insulin-induced amyloid polymerization and insulin.

[0056] (Test Example 3: Increase in anti-amyloid antibodies in insulin users) Long-term insulin users were examined for an increase in anti-amyloid antibodies. The table shows the cases examined. In the table, INSULIN indicates long-term insulin users, and NAIVE indicates insulin-naive subjects. The number of subjects (N(F), age, HbAlc, Cr, duration of insulin use, and MOCA score are shown in the table.

[0057]

[0058] Immunity was evaluated using ELISA for the serum in the same manner as in Test Example 2. Figure 3 is a graph showing the ELISA standard curve used in Test Example 3.

[0059] Figure 4 is a graph showing the results of a comparison of the evaluation of human plasma anti-amyloid β1-42 antibodies. Comparisons were performed using the Mann-Whitney U test (*p<0.05). As shown in the figure, long-term insulin users (INSULIN) had significantly increased anti-amyloid β1-42 antibodies compared to insulin-naive subjects (NAIVE). Plasma amyloid β-42 is known to be the highest risk group for Alzheimer's disease, and anti-amyloid β-42 antibodies were expressed in the insulin-administered group. These results suggest that anti-amyloid β antibodies are produced in the insulin-administered group by subcutaneous insulin-amyloid polymerization protein.

[0060] Although the embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be embodied in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as defined in the claims.

[0061] According to the present invention, it is possible to provide an insulin amyloid-polymerized protein, an antibody, an antibody-producing B cell, and a medical composition that can effectively treat and prevent Alzheimer's dementia with few side effects.

Claims

1. An insulin amyloid polymerization protein collected from a patient administered with insulin for use in treating a patient with Alzheimer's disease.

2. The insulin amyloid polymerization protein according to claim 1, wherein the collection is from the patient using three-dimensional information of the subcutaneous tissue of the patient.

3. An insulin amyloid polymerization protein composition for use in treating a patient with Alzheimer's disease, the insulin amyloid polymerization protein being obtained by chemically bonding insulin and amyloid.

4. The insulin amyloid polymerization protein according to claim 1 or 3 that does not cross-react with either an anti-insulin antibody or an anti-amyloid antibody.

5. An antibody that cross-reacts with the insulin amyloid polymerization protein according to claim 1.

6. The antibody according to claim 5, collected from the serum of a patient having the insulin amyloid polymerization protein.

7. An antibody-producing B cell that produces the antibody according to claim 5.

8. A medical composition for use in treating a patient with Alzheimer's disease, the medical composition comprising the insulin amyloid polymerization protein according to claim 1 or 3, or the antibody according to claim 5.

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