Localized tau imaging for the diagnosis and treatment of Alzheimer's disease

Abstract

A method is disclosed for using localized tau PET scanning to identify subjects suffering from or suspected of suffering from Alzheimer's disease, diagnose Alzheimer's disease, and treat Alzheimer's disease. The method is particularly useful for treating and diagnosing patients susceptible to and at risk of developing amyloid-β and cognitive impairment using tau PET imaging based on localized tau PET measurements.

Description

[Technical field]

[0001] The present disclosure relates generally to medicines. More specifically, the present disclosure relates to the diagnostic and / or therapeutic use of tau PET imaging to identify patients suffering from or susceptible to developing Alzheimer's disease. [Background technology]

[0002] Alzheimer's disease (AD) is a progressive brain disorder that gradually destroys memory and thinking abilities. AD is characterized by the formation of amyloid plaques, tau neurofibrillary tangles, and loss of neuronal connections in the brain. There are five related stages of Alzheimer's disease: preclinical Alzheimer's disease, Alzheimer's disease with mild cognitive impairment (AD with MCI), Alzheimer's disease with mild dementia, Alzheimer's disease with moderate dementia, and Alzheimer's disease with severe dementia. A subject may suffer from preclinical Alzheimer's disease before any symptoms appear. A subject with Alzheimer's disease with mild cognitive impairment manifests as mild changes in memory and thinking abilities. A subject with Alzheimer's disease with mild dementia experiences significant impairments in memory and thinking that affect daily functioning. A subject with Alzheimer's disease with moderate dementia becomes more confused and forgetful and begins to require more assistance with daily activities and self-care. In the stage of Alzheimer's disease with severe dementia, subjects may lose the ability to communicate coherently, may require daily assistance with personal care, and may experience a decline in physical abilities.

[0003] Diagnosis is generally based on the patient's medical history, cognitive testing, and medical imaging. Molecular imaging tracers for amyloid beta and tau are used to determine the distribution of amyloid beta and tau, respectively, in Alzheimer's disease and other neurodegenerative diseases. AD patients have both amyloid plaques and tau neurofibrillary tangles, but the interaction between amyloid beta (Aβ) and tau that leads to cognitive impairment is not well understood. Amyloid pathology is present in AD, but there is no consistent association with the severity of clinical features or duration of disease (see Villemagne et al., Ann Neurol. 2011;69:181-192). One theory suggests that elevated amyloid beta induces downstream tau hyperphosphorylation and aggregation, synaptic dysfunction, and neuronal loss that contributes to cognitive impairment. Another theory suggests that Aβ and abnormal tau are two independent factors that exert a synergistic effect on synaptic dysfunction and neuronal loss. It also remains difficult to determine whether patients who exhibit subtle cognitive symptoms have preclinical AD, which may progress to AD dementia. Early diagnosis and treatment can slow the clinical progression of AD and also allow for monitoring of response to treatment.

[0004] Thus, there is a continuing need to identify subjects with AD, stages of disease progression in AD patients, and treat subjects with or susceptible to AD. There is also a need for improved methods for determining whether a subject is responding to treatment. [Brief description of the drawings]

[0005] [Figure 1] FIG. 1 shows amyloid positivity in subjects from the A05 dataset (NCT02016560) using the PERSI criteria. [Diagram 2] 1 shows the amyloid positivity rate in subjects from the A05 dataset using the CereCrus criteria. [Diagram 3]1 shows amyloid positivity rates in subjects from the ADNI (Alzheimer's disease Neuroimaging Initiative) dataset using the CereCrus criteria. [Figure 4] 1 shows the SNR (signal-to-noise ratio) in subjects from the A05 dataset using the PERSI criterion. [Diagram 5] 1 shows the SNR in subjects from the A05 dataset using the CereCrus criterion. [Figure 6] 1 shows the SNR in subjects from the ADNI (Alzheimer's disease Neuroimaging Initiative) dataset using the CereCrus criterion. [Figure 7] 1 shows data from the A05 dataset for amyloid positivity in subjects, SNR in subjects, and correlations between regional SUVR and annual cognitive change, as described in Example 1, where r represents the Pearson correlation coefficient. [Figure 8] 1 shows data from the ADNI dataset for amyloid positivity in subjects, SNR in subjects, and correlations between regional SUVR and annual cognitive change, as described in Example 1, where r represents the Pearson correlation coefficient. [Figure 9] Shown is a scatter plot on the left showing ADsignatureSUVR versus EτVOI SUVR, with subjects color coded based on amyloid status, with Aβ+ in grey and Aβ− in black, and an expanded subsection on the right highlighting subjects in the Eτ+ / ADsignature− quadrant. [Figure 10] Boxplots showing 18-month change in (A) EτVOI SUVR, (B) ADsignature VOI SUVR, (C) cortical thickness, and (D) MMSE across quadrants, where Q1 corresponds to Eτ+ / ADsignature+, Q2 corresponds to Eτ+ / ADsignature-, and Q3 corresponds to Eτ- / ADsignature-. [Figure 11]Shown are scatter plots on the left showing Braak stage versus ADsignature VOI SUVR, where the horizontal dotted line represents the ADsignature positivity cutoff of 1.1059, and scatter plots on the right showing Braak status versus Eτ VOI SUVR, where the dotted line represents the Eτ VOI cutoff of 1.1052. Summary of the Invention

[0006] The present disclosure relates generally to the diagnostic and therapeutic use of tau imaging to identify patients suffering from and susceptible to developing Alzheimer's disease.

[0007] In one aspect, the disclosure relates to a method of treating a patient suffering from or suspected of suffering from Alzheimer's disease, the method comprising: analyzing a tau PET scan of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0008] In one aspect, the disclosure relates to a method of diagnosing a patient as having or suspected of having Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having Alzheimer's disease if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0009] In one aspect, the disclosure relates to a method of identifying a patient suffering from or suspected of suffering from Alzheimer's disease as a candidate patient for receiving Alzheimer's disease treatment, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0010] In one aspect, the disclosure relates to a method of treating a patient having or suspected of having amyloid plaques, the method comprising: analyzing tau images of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0011] In one aspect, the disclosure relates to a method of diagnosing a patient as having or suspected of having amyloid plaques, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having amyloid plaques if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0012] In one aspect, the disclosure relates to a method of identifying a patient having or suspected of having amyloid plaques as a candidate patient for receiving Alzheimer's disease treatment, the method comprising: analyzing a tau positron emission tomography (PET) scan of a brain region of the patient to determine a tau PET SUVR; and identifying the patient as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0013] In one aspect, the disclosure relates to a method of identifying cognitive decline in a patient affected or suspected of being affected by Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as having cognitive decline if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0014] In one aspect, the disclosure relates to a method of identifying whether a patient receiving Alzheimer's disease treatment is responding to the Alzheimer's disease treatment, the method including: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; administering the Alzheimer's disease treatment to the patient; analyzing a tau positron emission tomography (PET) scan of the brain region of the patient to determine a tau PET SUVR after administration of the Alzheimer's disease treatment; and identifying the patient as responding to the Alzheimer's disease treatment if the tau PET SUVR before administration of the Alzheimer's disease treatment has changed based on the determination of the tau PET SUVR after administration of the Alzheimer's disease treatment.

[0015] In one aspect, the disclosure relates to a method of determining tau burden in a patient affected or suspected of being affected with Alzheimer's disease, the method comprising analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR, and identifying the patient as having tau burden if the tau PET SUVR is greater than 1.15.

[0016] In one aspect, the disclosure relates to a method of determining whether a patient is a candidate for enrollment in an Alzheimer's disease clinical trial, the method comprising: analyzing tau positron emission tomography (PET) scans from a brain region of the patient to determine a region-based tau PET SUVR; and identifying the patient as a candidate for enrollment if the tau PET SUVR is greater than 1.15. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, the preferred methods and materials are described below.

[0018] While the present disclosure is susceptible to various modifications and alternative forms, exemplary embodiments are shown by way of example in the drawings and will be described in detail herein. However, it should be understood that the description of the exemplary embodiments is not intended to limit the present disclosure to the particular forms disclosed, but on the contrary, the intention is to embrace all modifications, equivalents, and alternatives falling within the scope of the present disclosure as defined by the above embodiments and the following claims. Therefore, to interpret the scope of the present disclosure, reference should be made to the above embodiments and the following claims.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, preferred methods and materials are described herein. Also, reference to an element by the indefinite article "a" or "an" does not exclude the possibility that there is a plurality of elements, unless the context clearly requires that there is one and only one element. Thus, the indefinite article "a" or "an" generally includes "at least one". The term "about" means up to ±10%.

[0020] As used herein, "susceptible" and "at risk" refer to having little resistance to a particular disease, disorder or condition, including having a genetic predisposition, having a family history of the disease, disorder or condition, and / or having symptoms of the disease, disorder or condition.

[0021] As used herein, a patient in need thereof (also used interchangeably with "subject"), in the context of the therapeutic uses herein, is a patient identified as needing or desiring medical intervention. Some embodiments of the methods of the present disclosure relate to a particular subset or subclass of identified patients (i.e., a subset or subclass of patients who are "in need" of assistance in addressing one or more specific conditions described herein), so not all patients are included in the subset or subclass of patients in need of treatment described herein. An effective amount is the amount of agent necessary to inhibit pathological diseases and disorders described herein. When at least one additional agent is administered to a patient, such agents may be administered sequentially, in parallel, or simultaneously to obtain the benefits of the agent. The term patient includes vertebrates, and is preferably a human patient.

[0022] In some embodiments, the biomarker 18F-flortaucipir, a PET ligand, may be used for purposes of this disclosure. PET tau images can be quantitatively assessed to estimate SUVR (standardized uptake value ratio), for example, by published methods (Pontecorvo et al., "A Multicentre Longitudinal Study of Flortaucipir (18F) in Normal Ageing, Mild Cognitive Impairment and Alzheimer's disease Dementia", Brain 142:1723-35 (2019); Devous et al., "Test-Retest Reproducibility for the Tau PET Imaging Agent Flortaucipir F18", Journal of Nuclear Medicine 59:937-43(2018); Southekal et al., "Flortaucipir F18 Quantitation Using Parametric Estimation of Reference Signal Intensity", J. Neurol. 1999, 14:131-132 (2018), which are incorporated by reference in their entirety). Nucl. Med. 59:944-51 (2018)), and / or can be quantitatively evaluated to visually evaluate the patient, for example, to determine whether the patient has a pathological diagnosis of Alzheimer's disease (Fleisher et al., "Positron Emission Tomography Imaging With F18-flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes," JAMA Neurology 77:829-39 (2020) which is incorporated by reference in its entirety).In this embodiment, SUVR was determined using a method similar to that published by Pontecorvo et al, "Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition," BRAIN 2017 doi:10.1093 / brain / aww334 pages 1-16, which is incorporated herein by reference. Lower SUVR values ​​indicate less tau binding and amyloid beta burden and slower AD progression, while higher SUVR values ​​indicate higher tau and amyloid beta burden and faster AD progression. In another embodiment, quantitative assessment from the flortaucipir scan is achieved by an automated image processing pipeline as described in Southekal et al., "Flortaucipir F18 Quantitation Using Parametric Estimation of Reference Signal Intensity," J. Nucl. Med. 59:944-951 (2018), which is incorporated by reference in its entirety.In some embodiments, counts in specific target regions of interest in the brain (e.g., Automated Anatomical Labeling (AAL) and / or MUBADA, see Pontecorv et al. "Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition", BRAIN 2017 doi:10.1093 / brain / aww334 pages 1-16; Devous et al., "Test-Retest Reproducibility for the Tau PET Imaging Agent Flortaucipir F18", J. Nucl. Med. 59:937-943 (2018)) are compared to a reference region, e.g., wholeCere, cerebellar GM (cereCrus), atlas-based white matter (atlasWM), subject-specific WM (ssWM, e.g., parametric estimate of reference signal intensity), and / or quantification of tau PET tau binding and amyloid burden, clinical diagnosis, age and cognition, BRAIN 2017 doi:10.1093 / brain / aww334 pages 1-16; Devous et al., "Test-Retest Reproducibility for the Tau PET Imaging Agent Flortaucipir F18", J. Nucl. Med. 59:937-943 (2018)). The preferred method for determining tau burden is quantitative analysis reported as the standardized uptake value ratio (SUVR), which represents counts in a specific target region of interest in the brain (e.g., MUBADA and / or AAL brain regions) compared to a reference region (e.g., cerebellar GM and / or PERSI).

[0023] As provided by the present disclosure, using region-based tau PET SUVR, patients can be identified as having and / or being susceptible to AD. Patients identified as having and / or being susceptible to AD can be administered treatment, and the patient's response to treatment can be monitored using region-based tau PET SUVR. As further provided by the present disclosure, using region-based tau PET SUVR, patients can be identified as being amyloid positive and / or being susceptible to amyloid positivity. Patients identified as being amyloid positive and / or being susceptible to amyloid positivity can be administered treatment, and the patient's response to treatment can be monitored using region-based tau PET SUVR. In addition, as provided by the present disclosure, using region-based tau PET SUVR, patients can also be identified as having and / or being susceptible to AD cognitive decline. As further provided in the present disclosure, using region-based tau PET SUVR, patients can be identified as candidates for treatment targeting amyloid plaques. Early identification of patients using region-based Tau PET SUVR may allow earlier therapeutic intervention and may prevent or slow disease progression. As provided by the present disclosure, using region-based Tau PET SUVR, patients may be identified as candidates for clinical trial eligibility and enrollment in customized AD trials.

[0024] In one aspect, the disclosure relates to a method of treating a patient suffering from or suspected of suffering from Alzheimer's disease, the method comprising: analyzing a tau PET scan of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0025] Tau positron emission tomography (tau PET) is performed by injection of a suitable tau PET tracer, such as 18F-labeled arylquinoline derivatives and 11C-labeled phenyl / pyridinyl-butadienyl-benzothiazole / benzothiazolium, 5H-pyrio[4,3-b]indole. Particularly suitable tau PET tracers include [18F]flortaucipir, [18F]RO948 (RO6958948), [11C]PBB3, [18F]MK-6240, [18F]PI-2620, [18F]GTP1, [18F]JNJ311 (JNJ64349311), [18F]JNJ067 (JNJ64326067), [18F]APN-1607 (PM-PBB3), and combinations thereof (see Bao et al. 2021:13(624330), which is incorporated herein by reference in its entirety). All brain regions are suitable for tau PET analysis. Particularly suitable brain regions include the central region, frontal lobe, temporal lobe, parietal lobe, occipital lobe, limbic lobe, insula, and subcortical gray matter nuclei (see Tzourio-Mazoyer et al., NeuroImage, 2002, 15:273-289, which is incorporated by reference in its entirety). In some embodiments, the method further comprises determining global tau PET.

[0026] The tau PET images are processed to obtain uniform image size and voxel dimensions. Standardized uptake value ratio (SUVR) images are generated using cerebellar gray matter and white matter as reference regions. It is particularly preferred to use white matter as the reference region to determine low tau, medium tau, and high tau. SUVR is calculated using an automated anatomical labeling (AAL) atlas or data-driven volumetrics of interest of brain regions (see Tzourio-Mazoyer et al., NeuroImage, 2002, 15:273-289, which is incorporated herein by reference in its entirety).

[0027] Amyloid positron emission tomography (amyloid PET) is performed by injection of amyloid PET tracers such as [18F]florbetapir, carbon-11 (11C) Pittsburgh compound B (11C-PiB), [18F]florbetaben, [18F]NAV4694 (AZD4694), and [18F]flutemetamol, and combinations thereof (see Bao et al., Aging Neurosci. 2021:13(624330), which is incorporated by reference in its entirety).

[0028] PET images were obtained using commercially available PET / computed tomography scanners such as Biograph mCT (Siemens), Biograph 6 Truepoint (Siemens), and Discovery 690 (GE Healthcare).

[0029] Magnetic resonance imaging (MRI) was performed with MRI images obtained using commercially available scanners such as a 3.0-T Discovery MR750 (GE Healthcare), a 3.0-T Tim Trio (Siemens), a 3.0-T Prisma (Siemens), and a 1.5-T Magnetom® Avanto (Siemens).

[0030] Cortical thickness is measured by methods known in the art, for example, by MRI.

[0031] The method further includes evaluating the SUVR images using multiblock barycentric discriminant analysis (MUBADA) to identify brain regions that provide the greatest diagnostic group differences. MUBADA was developed as a statistical method to predict group membership conditions from large data sets that are structured into coherent blocks (e.g., voxels) of variables when the data have many more variables than participants (typically the case for neuroimaging data). MUBADA is an extension of mean-centered partial least squares correlation and is often used in neuroimaging studies.

[0032] The method further includes evaluation of medical history, neurological examination, and neuropsychological testing, which generally includes brain plaque imaging, mental or cognitive evaluation, and functional evaluation. Suitable neuropsychological tests include the Clinical Dementia Rating-summary of boxes (CDR-SB), the Mini-Mental State Examination (MMSE), and the 13-item Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-Cognitive). 13 The MMSE is a diagnostic screening tool that measures cognitive abilities such as orientation to time and place, short-term episodic memory, attention, problem solving, visuospatial abilities, and language and motor skills. 13 The ADCS assesses cognition and differentiates between normal cognitive function and cognitive impairment, with lower scores representing less impairment and higher scores representing more impairment. Functional assessments include the Alzheimer's disease Cooperative Study-Activities of Daily Living (ADCS-ADL). Cognitive and functional assessments can be used to determine changes in a patient's cognition (e.g., cognitive decline) and function (e.g., functional decline).

[0033] As used herein, "treating" (or "treat" or "treatment") refers to a process that involves slowing, interrupting, preventing, controlling, halting, reducing, or reversing the progression or severity of an existing symptom, disorder, condition, or disease, but does not necessarily involve the complete elimination of all symptoms, conditions, or disorders associated with the disease associated with administering the treatment. As used herein, "preventing" refers to administering a treatment prophylactically to asymptomatic patients or patients with preclinical Alzheimer's disease to prevent the onset or progression of the disease. The normal range of amyloid plaques is defined as demonstrating an amyloid plaque level of 25 centiloids or less for two consecutive PET scans at least six months apart, or a single PET scan demonstrating a plaque level of less than 11 centiloids. In this disclosure, the term "normal range" of amyloid plaques in the brain is used interchangeably with "removed" brain amyloid plaques. In some embodiments, the disclosure slows the decline from baseline in a composite cognitive endpoint by about 15 to about 45 percent over about 4 weeks, about 8 weeks, about 12 weeks, about 16 weeks, about 20 weeks, about 24 weeks, about 28 weeks, about 32 weeks, about 36 weeks, about 40 weeks, about 44 weeks, about 48 weeks, about 52 weeks, about 56 weeks, about 60 weeks, about 64 weeks, about 68 weeks, about 72 weeks, or about 76 weeks. In some embodiments, the disclosure slows the decline or disease progression by about 15 to about 60 percent from baseline on the Integrated Alzheimer's disease Rating Scale (iADRS) or compared to untreated patients. The treatment is administered to the patient to slow disease progression. Disease progression will be measured by mixed-model repeated-measures (MMRM) models, Bayesian Disease Progression Model (DPM), the Unified Alzheimer's Disease Rating Scale from baseline or compared to untreated patients, and the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) from baseline or compared to untreated patients.

[0034] In some embodiments, the treatment results in a reduction or lowering of amyloid deposits, amyloid-β plaques, amyloid-β burden in the brain, and combinations thereof. In some embodiments, the treatment results in a reduction or lowering of tau levels in the brain. In some embodiments, the treatment results in a reduction, lowering, or prevention of further increase in tau burden in specific regions of the brain. In some embodiments, the treatment results in a reduction or lowering of tau levels in plasma. In some embodiments, such treatment results in a reduction or lowering of neurofilament light chain (NfL) levels in the brain of patients suffering from a disease characterized by Aβ plaques. In some embodiments, such treatment results in an increase in the Aβ42 / 40 ratio in the plasma or cerebrospinal fluid (CSF) of patients suffering from a disease characterized by Aβ plaques. In some embodiments, such treatment results in a reduction or lowering of glial fibrillary acidic protein (GFAP) in the blood of patients suffering from a disease characterized by Aβ plaques. In some embodiments, such treatment results in a decrease or reduction in P-tau217 levels in patients suffering from a disease characterized by Aβ plaques.

[0035] Alzheimer's disease treatments include anti-amyloid antibodies, anti-tau antibodies, and combinations thereof. Suitable Alzheimer's disease treatments include anti-Ab40 and 42 antibodies, N3pG targeting antibodies, OGAi (inhibitors of 3-O-(N-acetyl-D-glucosaminyl)-L-serine / threonine N-acetylglucosaminyl hydrolase, herein referred to as OGA) targeting antibodies and small molecules, tau targeting antibodies and small molecules. Some examples of these treatments include anti-N3pG antibodies (e.g., donanemab and N3pG IV or LY3372993), anti-amyloid beta antibodies (e.g., ADUHELM®, solanezumab, gantenerumab, and lecanemab).

[0036] Donanemab is an IgG1 monoclonal antibody against the N-terminal pyroglutamic acid modification of the third amino acid of the amyloid beta (N3pGlu Aβ) epitope, which is present only in brain amyloid beta plaques. The mechanism of action of donanemab is to target and remove existing amyloid plaques. Methods for making and using donanemab are described in U.S. Patent Nos. 8,679,498 and 8,961,972, which are expressly incorporated herein by reference (therein referred to as antibody B12L). Suitable dosing (as described in International Application Nos. PCT / US2017 / 038999 and PCT / US2022 / 011894, expressly incorporated herein by reference) includes, among others, about 100 mg to about 700 mg three times every four weeks (i.e., once every four weeks), followed by about 700 mg to about 1400 mg once every four weeks. The dosing regimen may be delivered for 1) up to 72 weeks, 2) until the patient is determined to be amyloid negative by PET, 3) until amyloid is determined to be cleared by PET, or 4) for an extended period of time. In some embodiments, a human subject is administered an anti-N3pGlu Aβ antibody (e.g., including a first dose and / or a second dose) for a period of time sufficient to bring amyloid plaques in the subject's brain into the normal range (or until brain amyloid plaques are cleared). In this disclosure, the term "normal range" of amyloid plaques in the brain is used interchangeably with "cleared" brain amyloid plaques. Normal range of amyloid plaques is defined as demonstrating amyloid plaque levels of 25 centiloids or less for two consecutive PET scans at least 6 months apart, or a single PET scan demonstrating a plaque level of less than 11 centiloids. In one embodiment, 700 mg of donanemab is administered every 4 weeks for the first three doses, followed by a dose of 1400 mg every 4 weeks until brain amyloid plaques are cleared. In some embodiments, the antibody has the following sequence:

[0037] SEQ ID NO:1 Light chain: DIVMTQTPLSLSVTPGQPASISCKSSQSLLYSRGKTYLNWLLQKPGQSPQLLIYAVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCVQGTHYPFTFGQGTKL EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[0038] SEQ ID NO:2 Heavy Chain: QVQLVQSGAEVKKPGSSVKVSCKASGYDFTRYYINWVRQAPGQGLEWMGWINPGSGNTKYNEKFKGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGITVYWGQGTTV TVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

[0039] N3pG IV or LY3372993 is an IgG1 monoclonal antibody against the N3pGlu Aβ epitope, and targets the removal of existing amyloid plaques. Methods for making and using LY3372993 are described in U.S. Patent Nos. 10,647,759 and 11,078,261, which are expressly incorporated herein by reference in their entirety (therein referred to as antibody 201c). In some embodiments, the antibody has the following sequence:

[0040] SEQ ID NO:3 Light chain: DIQMTQSPSTLSASVGDRVTITCRASQSLGNWLAWYQQKPGKAPKLLIYQASTLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYKGSFWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[0041] SEQ ID NO:4 Heavy Chain: EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGGSGSYYNGFDYW GQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

[0042] ADUHELM® (aducanumab-avwa) is an amyloid beta-directed antibody indicated for the treatment of Alzheimer's disease. Suitable doses include 10 mg / kg administered as an intravenous infusion every 4 weeks.

[0043] Solanezumab selectively binds to soluble amyloid beta (Aβ) to promote the clearance of Aβ. Suitable doses of solanezumab include 400 mg to 1600 mg (preferably 1600 mg) intravenously every 4 weeks. Solanezumab (including methods of making and using solanezumab) is described in the following patent documents, which are expressly incorporated herein by reference: U.S. Pat. No. 7,195,761; U.S. Patent Application Publication No. 20060039906; U.S. Pat. Nos. 7,892,545, 8,591,894, 7,771,722; and U.S. Patent Application Publication No. 20070190046. Those skilled in the art will recognize that solanezumab is an IgG1 monoclonal antibody with CDRs. Solanezumab binds to the central domain of the Aβ peptide. In some embodiments, the antibody has the following sequence:

[0044] SEQ ID NO:5 Light chain: DVVMTQSPLSLPVTLGQPASISCRSSQSLIYSDGNAYLHWFLQKPGQSPRLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHVPWTFGQGTKV EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[0045] SEQ ID NO:6 Heavy Chain: EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYSMSWVRQAPGKGLELVAQINSVGNSTYYPDTVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCASGDYWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0046] Antibodies of the foregoing sequences (as well as those of the patents mentioned above in the following patent documents: U.S. Pat. No. 7,195,761, U.S. Patent Application Publication No. 20060039906, U.S. Pat. Nos. 7,892,545, 8,591,894, 7,771,722, U.S. Patent Application Publication No. 20070190046) may be formulated and referred to as solanezumab. Thus, this embodiment includes the antibodies of SEQ ID NOs: 1 and 2 or other antibodies, as well as antibodies formulated in a composition called solanezumab. One of skill in the art will understand that either can be used.

[0047] Lecanemab (BAN2401) is a humanized monoclonal antibody administered to slow the progression of Alzheimer's disease by neutralizing and eliminating soluble Aβ aggregates (protofibrils) that may contribute to the neurodegenerative process. A suitable dose of lecanemab includes 10 mg / kg body weight.

[0048] LY3372689, N-[4-fluoro-5-[[(2S,4S)-2-methyl-4-[(5-methyl-1,2,4-oxadiazol-3-yl)-methoxy]-1-piperidyl]methyl]thiazol-2-yl]acetamide, is a small molecule inhibitor of O-GlcNAcase and is believed to reduce tau pathology and associated neurodegeneration. Methods for preparing and using LY3372689 are described in U.S. Pat. No. 10,081,625, which is expressly incorporated herein by reference. Those skilled in the art will recognize that pharma- ceutically acceptable salts of LY3372689 may be prepared for pharmaceutical use, and formulations that include one or more pharma-ceutically acceptable carriers, diluents, or excipients may be used in the manufacture of medicaments. Thus, the present embodiment includes the following structure of LY3372689, which may be prepared as a pharma-ceutically acceptable salt form and formulated into a composition referred to as LY3372689: One skilled in the art will understand that all of the dosages of this molecule can be used as disclosed in WO 2022 / 020663. [ka]

[0049] Suitable brain regions are described herein.

[0050] When the brain region is the inferior temporal brain region, the Tau PET SUVR ranges from about 1.05 to about 1.45. In some embodiments, when the brain region is the inferior temporal brain region, the Tau PET SUVR is about 1.45. When the brain region is the lateral temporal brain region, the Tau PET SUVR ranges from about 1.35 to about 1.45. When the brain region is the middle and superior temporal brain region, the Tau PET SUVR ranges from about 1.35 to about 1.45. When the brain region is the lateral parietal brain region, the Tau PET SUVR ranges from about 1.10 to about 1.45. When the brain region is the bilateral entorhinal cortex, the Tau PET SUVR ranges from about 1.05 to about 1.45. When the brain region is the fusiform gyrus, the Tau PET SUVR ranges from about 1.05 to about 1.45. When the brain region is the parahippocampal gyrus, the Tau PET SUVR ranges from about 1.05 to about 1.45.

[0051] In some embodiments, the method may further comprise analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0052] In some embodiments, the method may further include determining cortical thickness.

[0053] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0054] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0055] In some embodiments, the method may further include obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0056] In another aspect, the disclosure relates to a method of diagnosing a patient as having or suspected of having Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having Alzheimer's disease if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0057] Suitable brain regions are described herein.

[0058] In some embodiments, a patient is diagnosed with or suspected of having Alzheimer's disease when the brain region is the inferior temporal brain region and the tau PET SUVR is 1.45. In some embodiments, a patient is diagnosed with or suspected of having Alzheimer's disease when the brain region is the lateral temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is diagnosed with or suspected of having Alzheimer's disease when the brain region is the mid and superior temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is diagnosed with or suspected of having Alzheimer's disease when the brain region is the lateral parietal region and the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0059] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0060] In some embodiments, the method may further include determining cortical thickness.

[0061] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0062] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0063] In some embodiments, the patient has or is suspected of having amyloid plaques.

[0064] In some embodiments, the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0065] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0066] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0067] In another aspect, the disclosure relates to a method of identifying a patient suffering from or suspected of suffering from Alzheimer's disease as a candidate patient for receiving Alzheimer's disease treatment, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0068] Suitable brain regions are described herein.

[0069] In some embodiments, the patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the brain region is the inferior temporal brain region and the tau PET SUVR is 1.45. In some embodiments, the patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the brain region is the lateral temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the brain region is the mid and superior temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the brain region is the lateral parietal brain region and the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0070] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0071] In some embodiments, the method may further include determining cortical thickness.

[0072] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0073] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0074] In some embodiments, the patient has or is suspected of having amyloid plaques.

[0075] In some embodiments, the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0076] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0077] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0078] In another aspect, the disclosure relates to a method of treating a patient having or suspected of having amyloid plaques, the method comprising: analyzing tau images of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0079] Suitable brain regions are described herein.

[0080] In some embodiments, the patient is identified as having amyloid plaques when the brain region is the inferior temporal brain region and the tau PET SUVR is 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the lateral temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the mid and superior temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the lateral parietal brain region and the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0081] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0082] In some embodiments, the method may further include determining cortical thickness.

[0083] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0084] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0085] In some embodiments, the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0086] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0087] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0088] In one aspect, the disclosure relates to a method of diagnosing a patient as having or suspected of having amyloid plaques, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having amyloid plaques if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0089] Suitable brain regions are described herein.

[0090] In some embodiments, the patient is identified as having amyloid plaques when the brain region is the inferior temporal brain region and the tau PET SUVR is 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the lateral temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the mid and superior temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the lateral parietal brain region and the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0091] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0092] In some embodiments, the method may further include determining cortical thickness.

[0093] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0094] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0095] In some embodiments, the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0096] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0097] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0098] In one aspect, the disclosure relates to a method of identifying a patient having or suspected of having amyloid plaques as a candidate patient for receiving Alzheimer's disease treatment, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0099] Suitable brain regions are described herein.

[0100] In some embodiments, the patient is identified as having amyloid plaques when the brain region is the inferior temporal brain region and the tau PET SUVR is 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the lateral temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the mid and superior temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having amyloid plaques when the brain region is the lateral parietal brain region and the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0101] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0102] In some embodiments, the method may further include determining cortical thickness.

[0103] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0104] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0105] In some embodiments, the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0106] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0107] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0108] In another aspect, the disclosure relates to a method of treating a patient having or suspected of having Alzheimer's disease cognitive decline, the method comprising: analyzing tau images of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0109] Suitable brain regions are described herein.

[0110] In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the inferior temporal brain region and the tau PET SUVR is 1.45. In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the lateral temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the mid and superior temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the lateral parietal brain region and the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0111] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0112] In some embodiments, the method may further include determining cortical thickness.

[0113] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0114] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0115] In some embodiments, the patient has or is suspected of having amyloid plaques.

[0116] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0117] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0118] In one aspect, the disclosure relates to a method of diagnosing a patient as having or suspected of having Alzheimer's disease cognitive decline, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having Alzheimer's disease cognitive decline if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0119] Suitable brain regions are described herein.

[0120] In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the inferior temporal brain region and the tau PET SUVR is 1.45. In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the lateral temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the mid and superior temporal brain region and the tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is identified as having Alzheimer's cognitive decline when the brain region is the lateral parietal brain region and the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0121] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0122] In some embodiments, the method may further include determining cortical thickness.

[0123] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0124] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0125] In some embodiments, the patient has or is suspected of having amyloid plaques.

[0126] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0127] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0128] In one aspect, the disclosure relates to a method of identifying cognitive decline in a patient affected or suspected of being affected by Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as having cognitive decline if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0129] In some embodiments, the patient is identified as having cognitive decline if the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45. In some embodiments, the patient is identified as having cognitive decline if the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having cognitive decline if the brain region is the mid and superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as having cognitive decline if the brain region is the lateral parietal brain region and the Tau PET SUVR is about 1.10 to about 1.45.

[0130] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0131] In some embodiments, the method may further include determining cortical thickness.

[0132] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0133] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0134] In some embodiments, the patient has or is suspected of having amyloid plaques.

[0135] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0136] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0137] In another aspect, the disclosure relates to a method of identifying whether a patient undergoing Alzheimer's disease treatment is responding to the Alzheimer's disease treatment, the method including: analyzing a tau PET scan from a brain region of the patient to determine a tau PET SUVR, administering the Alzheimer's disease treatment to the patient, analyzing a tau PET scan from the brain region of the patient to determine a tau PET SUVR after administration of the Alzheimer's disease treatment, and identifying the patient as responding to the Alzheimer's disease treatment if the tau PET SUVR before administration of the Alzheimer's disease treatment has changed based on the determination of the tau PET SUVR after administration of the Alzheimer's disease treatment.

[0138] Alzheimer's disease treatments are described herein.

[0139] Suitable brain regions are described herein.

[0140] In some embodiments, the patient is identified as responding when the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45. In some embodiments, the patient is identified as responding when the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as responding when the brain region is the mid and superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, the patient is identified as responding when the brain region is the lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0141] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0142] In some embodiments, the method may further include determining cortical thickness.

[0143] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0144] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0145] The method may further include analyzing the patient for amyloid plaques before and after administering the Alzheimer's disease treatment.

[0146] The method may further include analyzing the patient for cognitive decline before and after administering an Alzheimer's disease treatment.

[0147] In another aspect, the disclosure relates to a method of determining tau burden in a patient suffering from or suspected of suffering from Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as having tau burden if the tau PET SUVR is greater than 1.15.

[0148] Suitable brain regions are described herein.

[0149] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0150] In some embodiments, the method may further include determining cortical thickness.

[0151] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0152] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0153] In some embodiments, the patient has or is suspected of having amyloid plaques.

[0154] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0155] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0156] In one embodiment, the brain region is the inferior temporal brain region and the Tau PET SUVR is greater than 1.40. In one embodiment, the brain region is the lateral temporal brain region and the Tau PET SUVR is greater than 1.30. In one embodiment, the brain region is the mid and superior temporal brain region and the Tau PET SUVR is greater than 1.30. In one embodiment, the brain region is the lateral parietal brain region and the Tau PET SUVR is greater than 1.15.

[0157] In one aspect, the disclosure relates to a method for determining whether a patient is a candidate for enrollment in an Alzheimer's disease clinical trial, the method comprising: analyzing tau positron emission tomography (PET) scans from a brain region of the patient to determine a region-based tau PET SUVR; and identifying the patient as a candidate for enrollment if the tau PET SUVR is greater than 1.15.

[0158] Suitable brain regions are described herein.

[0159] In some embodiments, a patient is identified as an enrollment candidate if the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45. In some embodiments, a patient is identified as an enrollment candidate if the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is identified as an enrollment candidate if the brain region is the mid and superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45. In some embodiments, a patient is identified as an enrollment candidate if the brain region is the lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0160] The method may further include analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0161] In some embodiments, the method may further include determining cortical thickness.

[0162] In some embodiments, the method may further include analyzing cerebrospinal fluid for amyloid beta.

[0163] In some embodiments, the method may further comprise analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0164] In some embodiments, the patient has or is suspected of having amyloid plaques.

[0165] In some embodiments, the methods may further include administering an Alzheimer's disease therapy as disclosed herein.

[0166] In some embodiments, the method further includes obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

[0167] In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is in the range of about 1.10 to about 1.45. In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is about 1.10. In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is about 1.15. In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is about 1.20. In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is about 1.25. In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is about 1.30. In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is about 1.35. In some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the Tau PET SUVR is about 1.40, hi some embodiments, a patient is identified as a candidate patient for receiving Alzheimer's disease treatment if the Tau PET SUVR is about 1.45. EXAMPLES

[0168] Example 1. Prognostic value of regional tau PET measurements in Alzheimer's disease Dataset: A05 test dataset (NCT02016560) N=35 AD and N=73 participants 18 Subjects in the confirmation cohort (A05C) of the Phase 2 / 3 study of F-AV-1451-A05 (flortaucipir) Subjects with 18-month follow-up data on the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) score ADNI Dataset N=24 AD and N=76 MCI participants Subjects who had a baseline ADAS-Cog13 assessment with long-term follow-up of 2-3 years Subjects with at least one tau PET (flortaucipir) scan at baseline and a florbetapir (FBP) scan within 6 months of the baseline ADAS-Cog13 assessment The demographic characteristics of the ADNI and A05 cohorts are shown in the table below.

[0169] [Table 1]

[0170] method: Tau burden (standardized uptake value ratio, SUVR) was quantified using AAL brain atlas-based temporal and parietal and AD-specific weighted cortical complex regions (MUBADA) referenced to parametric estimation of reference signal intensity (PERSI) in the cerebellar crus region (cereCrus) and white matter.

[0171] For all global and region-based tau SUVRs, subjects were dichotomized into high (T+) and low (T-) tau groups using a series of thresholds (1.0-1.5). Signal-to-noise ratio (SNR) of cognitive decline and florbetapir-based amyloid positivity (quantitative threshold) were assessed for each T+ group based on regional and composite tau PET measurements. SNR was defined as the mean annualized ADAS-Cog score change / ADAS-Cog score standard deviation.

[0172] result: As shown by the data in Figures 1-6, regional tau PET measurements are prognostic of cognitive decline and predictive of amyloid positivity as assessed by florbetapir (FBP).

[0173] Regional tau PET analysis showed that using temporal and parietal SUVR values ​​can help classify patients by risk of cognitive decline and amyloid status, and therefore clinical trial eligibility algorithms can be implemented using regional tau criteria. Regional tau PET measurements correlate with annual cognitive change (data from the A05 dataset are presented in FIG. 7 and data from the ADNI dataset are presented in FIG. 8, where "r" represents Pearson's correlation coefficient) and may be superior to combined tau PET measurements in predicting cognitive decline and amyloid positivity.

[0174] Regional tau PET measurements were highly correlated with combined regional tau PET measurements (Pearson's r >0.95).

[0175] For all global and region-based flortaucipir measures, elevated SUVR thresholds resulted in lower mean MMSE scores, greater mean global tau burden, higher amyloid-positive patient rates, and increased mean cognitive decline in T+ patients. SUVR thresholds that identified subgroups with high amyloid-positive rates (>90%, Table 1 below) and high SNR (>1, Table 2 below) were observed to be lower for brain regions identified later in the tau pathological cascade: inferior temporal (1.45), lateral temporal (1.35), and lateral parietal (1.20).

[0176] [Table 2]

[0177] [Table 3]

[0178] The following references are incorporated by reference herein: [1] Ossenkoppele et al, JAMA Neurology, 2021, [2] Pontecorvo et al, Brain, 2019, [3] Devous et al, Journal of Nuclear medicine, 2018, [4] Southekal et al, Journal of Nuclear medicine, 2018.

[0179] Example 2. Early tau detection in flortaucipir images - validation in autopsy confirmed data and implications for disease progression There is growing interest in using tau PET to identify patients at an early stage of Alzheimer's disease (AD). In this example, we evaluated the combined temporal lobe (Eτ) VOI in a longitudinal flortau sipir cohort and compared it to previously described global neocortical territories. In a separate autopsy-confirmed study, we evaluated the sensitivity of the Eτ VOI for identifying intermediate (B2) neurofibrillary tangle (NFT) pathology.

[0180] Methods: 427 subjects received flortaucipir, florbetapir, MRI, and cognitive assessment at baseline and 18 months.

[0181] [Table 4] CN=normal cognition, MCI=mild cognitive impairment, AD=Alzheimer's disease, N=number of subjects, MMSE=Mini Mental Score Examination, F=female, and M=male. Age is expressed as mean ± standard deviation. MMSE is also expressed as mean ± standard deviation. CD=college degree or higher; HS=high school degree or less; C=Caucasian; NC=Asian, black or African American, or other; all 109 subjects who received solanezumab were amyloid positive and had mild to moderate cases of AD.

[0182] In another autopsy study, 67 subjects underwent flortaucipir testing antemortem, and neuropathological findings were recorded by two experts according to NIA-AA recommendations.

[0183] [Table 5] N is the number of subjects, age is expressed as mean ± SD, sex is indicated as female / male; CD = college graduate or above; HS = high school graduate or below; C = Caucasian; NC = Asian, Black or African American, or other.

[0184] Two VOIs: Eτ, which includes the Freesurfer volumes transformed into MNI space (bilateral entorhinal cortex, fusiform gyrus, parahippocampal gyrus, and inferior temporal gyrus), and the global AD signal-weighted neocortical area (MUBADA, AD signature SUVR relative to white matter reference regions (PERSI) was calculated using the PERSI (also called the PERSI-based SUVR cutoff). A positive SUVR cutoff was determined based on a cohort of young, cognitively normal subjects. Subjects were divided into groups based on T+ positivity for both VOIs (Eτ+ / AD signal+, Eτ+ / AD signal-, Eτ- / AD signal-). Baseline SUVR, 18-month change in SUVR, neurodegeneration, and cognition were compared between groups. For autopsy studies, the sensitivity of Eτ in identifying subjects with intermediate Braak pathology (B2) was compared to that of the AD signal-weighted neocortical VOI. To visually assess uptake, a mean surface map was generated for subjects in the Eτ+ / AD signal-group with B2 NFT scores.

[0185] Results: Of 390 analyzable subjects, 64 were identified as Eτ+ / AD signal-. 84% were Aβ+, 100% were diagnosed with MCI or AD, and 59% were APOE E4 carriers. Subjects positive for both Eτ and MUBADA VOI were represented in quadrant 1 (Q1), subjects positive for Eτ only were represented in quadrant 2 (Q2), subjects with low Eτ and low MUBADA were represented in quadrant 3 (Q3), and subjects with low Eτ and high MUBADA were represented in quadrant 4 (Q4) (Figure 9). As there were only two subjects in Q4, no analysis was performed for Q4. Consistent with the hypothesis that Eτ+ / AD signal- status reflects the early stage of AD, Eτ+ / AD signal- subjects deteriorated significantly faster than Eτ- / AD signal- subjects in most measures (i.e., change in AD signal VOI SUVR, EτVOI, cortical thickness, and MMSE) but significantly slower than Eτ+ / AD signal+ subjects (Figure 10). AD signal regions were selective for autopsy-treated subjects with B3 (Braak V / VI) NFT scores. In the autopsy study, 12 / 15 B2 subjects (including 10 / 11 Braak IV) were Eτ+ / AD signal- (Figure 11). Surface maps showed that flortaucipir uptake was largely captured by EτVOI regions in B2 subjects.

[0186] Summary: Eτ VOI identified subjects who were primarily amyloid positive (Aβ+), APOE E4 carriers, and diagnosed with MCI or AD, with increased temporal tau but not global tau (Eτ+ / AD signal-). Eτ+ / AD signal- subjects had greater tau accumulation, greater atrophy, and greater MMSE decline at 18 months compared to Eτ- / AD signal- subjects. Finally, Eτ VOI identified a majority of intermediate NFT score subjects in the autopsy confirmatory study. This study presents a visualization of premortem FTP retention patterns that are consistent at the group level with the neurofibrillary tangle staging scheme proposed by Braak. These findings suggest that Eτ VOI may be sensitive to detect impaired subjects early in the course of Alzheimer's disease.

[0187] Exemplary embodiments of the present disclosure The following provide additional embodiments described throughout this disclosure.

[0188] 1. A method of treating a patient suffering from or suspected of suffering from Alzheimer's disease, the method comprising: analyzing a tau PET scan of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0189] 2. The embodiment of 1, wherein the Alzheimer's disease treatment is selected from donanemab, N3pG IV or LY3372993, LY3372689, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0190] 3. The embodiment of any one of 1 or 2, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0191] 4. The embodiment of any one of 1-3, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR ranges from about 1.35 to about 1.45.

[0192] 5. The embodiment of any one of 1-4, wherein the brain region is the mid and upper temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0193] 6. The embodiment of any one of 1-5, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR ranges from about 1.10 to about 1.45.

[0194] 7. The embodiment of any one of 1-6, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0195] 8. The embodiment of any one of 1 to 7, further comprising determining cortical thickness.

[0196] 9. The embodiment of any one of 1-8, further comprising analyzing cerebrospinal fluid for amyloid beta.

[0197] 10. The embodiment of any one of 1 to 9, further comprising analyzing the ε4 allele of Apolipoprotein E (APOE E4) genotype.

[0198] 11. The embodiment of any one of 1-10, further comprising obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administering an Alzheimer's disease treatment.

[0199] 12. The embodiment of any one of 1-11, wherein the patient has or is suspected of having amyloid plaques.

[0200] 13. The embodiment of any one of 1-12, wherein the patient has or is suspected of having Alzheimer's disease cognitive decline.

[0201] 14. A method for diagnosing a patient as having or suspected of having Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having Alzheimer's disease if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0202] 15. The embodiment of claim 14, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0203] 16. The embodiment of any one of 14 or 15, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0204] 17. The embodiment of any one of 14-16, wherein the brain region is the mid and superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0205] 18. The embodiment of any one of 14-17, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR ranges from about 1.10 to about 1.45.

[0206] 19. The embodiment of any one of 14-18, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0207] 20. The embodiment of any one of 14-19, further comprising determining cortical thickness.

[0208] 21. The embodiment of any one of 14-20, further comprising analyzing cerebrospinal fluid for amyloid beta.

[0209] 22. The embodiment of any one of 14 to 21, further comprising analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0210] 23. The embodiment of any one of 14-22, further comprising administering to the patient an Alzheimer's disease therapy if the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0211] 24. The embodiment of any one of 14-23, wherein the patient has or is suspected of having amyloid plaques.

[0212] 25. The embodiment of any one of 14-24, wherein the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0213] 26. The embodiment of any one of 14-25, further comprising administering to the patient an Alzheimer's disease therapy.

[0214] 27. A method for identifying a patient suffering from or suspected of suffering from Alzheimer's disease as a candidate patient for receiving treatment for Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as a candidate patient for receiving treatment for Alzheimer's disease if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0215] 28. The embodiment of 27, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0216] 29. The embodiment of any one of 27 or 28, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0217] 30. The embodiment of any one of 27-29, wherein the brain region is the mid+superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0218] 31. The embodiment of any one of 27-30, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR ranges from about 1.10 to about 1.45.

[0219] 32. The embodiment of any one of 27-31, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0220] 33. The embodiment of any one of 27-32, further comprising determining cortical thickness.

[0221] 34. The embodiment of any one of 27-33, further comprising analyzing cerebrospinal fluid for amyloid beta.

[0222] 35. The embodiment of any one of 27-34, further comprising analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0223] 36. The embodiment of any one of 27-35, wherein the patient has or is suspected of having amyloid plaques.

[0224] 37. The embodiment of any one of 27-36, wherein the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0225] 38. The embodiment of any one of 27-38, further comprising administering to the patient an Alzheimer's disease therapy.

[0226] 39. A method of treating a patient having or suspected of having amyloid plaques, the method comprising: analyzing tau images of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0227] 40. The embodiment of 39, wherein the Alzheimer's disease treatment is selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0228] 41. The embodiment of any one of 39 or 40, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0229] 42. The embodiment of any one of 39-41, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0230] 43. The embodiment of any one of 39-42, wherein the brain region is the mid and superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0231] 44. The embodiment of any one of 39-43, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR ranges from about 1.10 to about 1.45.

[0232] 45. The embodiment of any one of 39-44, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0233] 46. ​​The embodiment of any one of 39 to 45, further comprising determining cortical thickness.

[0234] 47. The embodiment of any one of 39-46, further comprising analyzing cerebrospinal fluid for amyloid beta.

[0235] 48. The embodiment of any one of 39-47, further comprising analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0236] 49. The embodiment of any one of 39-48, wherein the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0237] 50. The embodiment of any one of 39-49, further comprising obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administering an Alzheimer's disease treatment.

[0238] 51. A method for diagnosing a patient as having or suspected of having amyloid plaques, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having amyloid plaques if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0239] 52. The embodiment of 51, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0240] 53. The embodiment of 51 or 52, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0241] 54. The embodiment of any one of 51-53, wherein the brain region is the mid and superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0242] 55. The embodiment of any one of 51-54, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0243] 56. The embodiment of any one of 51-55, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0244] 57. The embodiment of any one of 51-56, further comprising determining cortical thickness.

[0245] 58. The embodiment of any one of 51-57, further comprising analyzing cerebrospinal fluid for amyloid beta.

[0246] 59. The embodiment of any one of 51-58, further comprising analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0247] 60. The embodiment of any one of 51-59, further comprising administering to the patient an Alzheimer's disease therapy if the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0248] 61. The embodiment of any one of 51-60, wherein the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0249] 62. The embodiment of any one of 51-60, further comprising obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administering an Alzheimer's disease treatment.

[0250] 63. A method for identifying a patient having or suspected of having amyloid plaques as a candidate patient for receiving treatment for Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as a candidate patient for receiving treatment for Alzheimer's disease if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0251] 64. The embodiment of 63, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0252] 65. The embodiment of any one of 63 or 64, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0253] 66. The embodiment of any one of 63 or 64, wherein the brain region is the mid+superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0254] 67. The embodiment of any one of 63-66, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0255] 68. The embodiment of any one of 63-67, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0256] 69. The embodiment of any one of 63-68, further comprising determining cortical thickness.

[0257] 70. The embodiment of any one of 63-69, further comprising analyzing cerebrospinal fluid for amyloid beta.

[0258] 71. The embodiment of any one of 63-70, further comprising analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0259] 72. The embodiment of any one of 63-71, wherein the patient has or is suspected of having Alzheimer's disease cognitive decline.

[0260] 73. The embodiment of any one of 63-72, further comprising obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administering an Alzheimer's disease treatment.

[0261] 74. A method for identifying cognitive decline in a patient suffering from or suspected of suffering from Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as having cognitive decline if the tau PET SUVR is in the range of about 1.10 to about 1.45.

[0262] 75. The embodiment of claim 74, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0263] 76. The embodiment of any one of 74 or 75, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0264] 77. The embodiment of any one of 74-76, wherein the brain region is the mid and superior temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0265] 78. The embodiment of any one of 74-77, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0266] 79. The embodiment of any one of 74-78, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

[0267] 80. The embodiment of any one of 74-79, further comprising determining cortical thickness.

[0268] 81. The embodiment of any one of 74-80, further comprising analyzing cerebrospinal fluid for amyloid beta.

[0269] 82. The embodiment of any one of 74-81, further comprising analyzing the ε4 allele of apolipoprotein E (APOE E4) genotype.

[0270] 83. The embodiment of any one of 74-82, wherein the patient has or is suspected of having amyloid plaques.

[0271] 84. The embodiment of any one of 74-83, further comprising obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administering an Alzheimer's disease treatment.

[0272] 85. A method for identifying whether a patient receiving Alzheimer's disease treatment is responding to the Alzheimer's disease treatment, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; administering the Alzheimer's disease treatment to the patient; analyzing a tau positron emission tomography (PET) scan from the brain region of the patient to determine a tau PET SUVR after administration of the Alzheimer's disease treatment; and identifying the patient as responding to the Alzheimer's disease treatment if the tau PET SUVR before administration of the Alzheimer's disease treatment has changed based on determining the tau PET SUVR after administration of the Alzheimer's disease treatment.

[0273] 86. The embodiment of claim 85, wherein the brain region is the inferior temporal brain region and has a Tau PET SUVR of less than 1.45 after administration of Alzheimer's disease treatment.

[0274] 87. The embodiment of any one of 85 or 86, wherein the brain region is the lateral temporal brain region and has a Tau PET SUVR of less than about 1.35 after administration of Alzheimer's disease treatment.

[0275] 88. The embodiment of any one of 85-87, wherein the brain regions are the mid and superior temporal brain regions and the Tau PET SUVR after administration of Alzheimer's disease treatment is less than 1.35.

[0276] 89. The embodiment of any one of 85-88, wherein the brain region is the lateral parietal brain region and has a Tau PET SUVR of less than 1.10 after administration of Alzheimer's disease treatment.

[0277] 90. The embodiment of any one of 85-89, wherein the patient has or is suspected of having amyloid plaques.

[0278] 91. The embodiment of any one of 85-90, wherein the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0279] 92. A method for determining tau burden in a patient suffering from or suspected of suffering from Alzheimer's disease, the method comprising: analyzing a tau positron emission tomography (PET) scan from a brain region of the patient to determine a tau PET SUVR; and identifying the patient as having tau burden if the tau PET SUVR is greater than 1.15.

[0280] 93. The embodiment of 92, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is greater than 1.40.

[0281] 94. The embodiment of any one of 92 or 93, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is greater than 1.30.

[0282] 95. The embodiment of any one of 92-94, wherein the brain region is the mid and superior temporal brain region and the Tau PET SUVR is greater than about 1.30.

[0283] 96. The embodiment of any one of 92-95, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR is greater than 1.15.

[0284] 97. The embodiment of any one of 92-96, wherein the patient has or is suspected of having amyloid plaques.

[0285] 98. The embodiment of any one of 92-97, wherein the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0286] 99. The embodiment of any one of 92-98, further comprising administering to the patient an Alzheimer's disease therapy.

[0287] 100. A method for determining whether a patient is a candidate for enrollment in a clinical trial for Alzheimer's disease, the method comprising: analyzing tau positron emission tomography (PET) scans from a brain region of the patient to determine a region-based tau PET SUVR; and identifying the patient as a candidate for enrollment if the tau PET SUVR is greater than 1.15.

[0288] 101. The embodiment of 100, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is greater than 1.40.

[0289] 102. The embodiment of any one of 100 or 101, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is greater than 1.30.

[0290] 103. The embodiment of any one of 100 to 102, wherein the brain region is the mid and superior temporal brain region and the Tau PET SUVR is greater than about 1.30.

[0291] 104. The embodiment of any one of 100 to 103, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR is greater than 1.15.

[0292] 105. The embodiment of any one of 100 to 104, wherein the patient has or is suspected of having amyloid plaques.

[0293] 106. The embodiment of any one of 100 to 105, wherein the patient has or is suspected of having cognitive decline due to Alzheimer's disease.

[0294] 107. The embodiment of any one of 100-106, further comprising administering to the patient an Alzheimer's disease therapy.

[0295] 100. The embodiment of any one of 100-107, further comprising analyzing the patient for mild cognitive impairment, Alzheimer's disease, amyloid beta, APOE E4 genotype, and combinations thereof.

[0296] 101. The embodiment of any one of 100-108, further comprising determining tau in a plasma sample, cerebrospinal fluid, or a combination thereof from the patient.

[0297] 110. A method of treating Alzheimer's disease in a patient identified as amyloid positive comprising administering an Alzheimer's disease treatment, wherein the patient is identified as amyloid positive based on a tau PET scan.

[0298] 111. The embodiment of 110, further comprising identifying the patient as at risk for cognitive decline by tau PET scanning.

[0299] 112. The embodiment of 110 or 111, wherein the Alzheimer's disease treatment is selected from donanemab, ADUHELM®, solanezumab, and lecanemab.

[0300] 113. The embodiment of any one of 110-112, wherein the Tau PET scan examines the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0301] 114. The embodiment of any one of 110-113, wherein the Tau PET scan examines a lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0302] 115. The embodiment of any one of 110-114, wherein the Tau PET scan examines mid and superior temporal brain regions and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0303] 116. The embodiment of any one of 110-115, wherein the Tau PET scan examines a lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0304] 117. A method of treating Alzheimer's disease in a patient identified as being at risk for Alzheimer's cognitive decline, wherein the patient is identified as being at risk by a tau PET scan.

[0305] 118. The embodiment of 117, further comprising identifying the patient as amyloid positive based on a tau PET scan.

[0306] 119. The embodiment of 117 or 118, wherein the Alzheimer's disease treatment is selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0307] 120. The embodiment of any one of 117-119, wherein the Tau PET scan examines the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0308] 121. The embodiment of any one of 117-120, wherein the Tau PET scan examines a lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0309] 122. The embodiment of any one of 117-121, wherein the Tau PET scan examines mid and superior temporal brain regions and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0310] 123. The embodiment of any one of 117-122, wherein the Tau PET scan examines a lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0311] 124. A method for determining that a patient is at risk for cognitive decline comprising performing a tau PET scan, wherein the patient is determined to be at risk based on SUVR levels in a particular brain region and / or at a particular level.

[0312] 125. The embodiment of 124, further comprising determining whether the patient is amyloid positive based on a tau PET scan.

[0313] 126. The embodiment of 124 or 125, further comprising administering to the patient an Alzheimer's disease treatment, wherein the treatment is selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0314] 127. The embodiment of any one of 124-126, wherein the Tau PET scan examines the inferior temporal brain region and the Tau PET SUVR is 1.45.

[0315] 128. The embodiment of any one of 124-127, wherein the Tau PET scan examines a lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0316] 129. The embodiment of any one of 124-128, wherein the Tau PET scan examines mid and superior temporal brain regions and the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0317] 130. The embodiment of any one of 124-129, wherein the Tau PET scan examines a lateral parietal brain region and the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0318] 131. A method of treating Alzheimer's disease in a patient, comprising identifying the patient as amyloid positive based on a tau PET scan, and administering treatment to the patient if the tau PET scan is above a threshold.

[0319] 132. The embodiment of 131, further comprising identifying the patient as at risk for Alzheimer's cognitive decline based on a tau PET scan.

[0320] 133. The embodiment of any one of 131-132, wherein the treatment is selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0321] 134. The embodiment of any one of 131-133, wherein the Tau PET scan examines the inferior temporal brain region and the threshold is a Tau PET SUVR of 1.45.

[0322] 135. The embodiment of any one of 131-134, wherein the Tau PET scan examines the lateral temporal brain region and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0323] 136. The embodiment of any one of 131-135, wherein the Tau PET scan examines mid and superior temporal brain regions and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0324] 137. The embodiment of any one of 131-136, wherein the Tau PET scan examines the lateral parietal brain region and the threshold is a Tau PET SUVR in the range of about 1.10 to about 1.45.

[0325] 138. A method of treating Alzheimer's disease in a patient, comprising identifying the patient as at risk for Alzheimer's cognitive decline based on a tau PET scan, and administering treatment to the patient if the tau PET scan is above a threshold.

[0326] 139. The embodiment of 138, further comprising identifying the patient as amyloid positive based on a tau PET scan.

[0327] 140. The embodiment of any one of 138-139, wherein the treatment is selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0328] 141. The embodiment of any one of 138-140, wherein the Tau PET scan examines the inferior temporal brain region and the threshold is a Tau PET SUVR of 1.45.

[0329] 142. The embodiment of any one of 138-141, wherein the Tau PET scan examines the lateral temporal brain region and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0330] 143. The embodiment of any one of 138-142, wherein the Tau PET scan examines mid and superior temporal brain regions and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0331] 144. The embodiment of any one of 138-143, wherein the Tau PET scan examines the lateral parietal brain region and the threshold is a Tau PET SUVR in the range of about 1.10 to about 1.45.

[0332] 145. A method of determining that a patient is amyloid positive comprising performing a tau PET scan, wherein the patient is determined to be amyloid positive if the tau PET scan is above a certain threshold.

[0333] 146. The embodiment of claim 145, wherein the Tau PET scan examines the inferior temporal brain region and the threshold is a Tau PET SUVR of 1.45.

[0334] 147. The embodiment of any one of 145-146, wherein the Tau PET scan examines the lateral temporal brain region and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0335] 148. The embodiment of any one of 145-147, wherein the Tau PET scan examines mid and superior temporal brain regions and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0336] 149. The embodiment of any one of 145-148, wherein the Tau PET scan examines the lateral parietal brain region and the threshold is a Tau PET SUVR in the range of about 1.10 to about 1.45.

[0337] 150. The embodiment of any one of 145-149, further comprising determining that the patient is at risk for Alzheimer's cognitive decline based on the tau PET scan being above a threshold.

[0338] 151. A method for determining that a patient is at risk for Alzheimer's cognitive decline, comprising performing a tau PET scan, wherein the patient is determined to be at risk for Alzheimer's cognitive decline if the tau PET scan is above a particular threshold.

[0339] 152. The embodiment of claim 151, wherein the Tau PET scan examines the inferior temporal brain region and the threshold is a Tau PET SUVR of 1.45.

[0340] 153. The embodiment of any one of 151-152, wherein the Tau PET scan examines the lateral temporal brain region and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0341] 154. The embodiment of any one of 151-153, wherein the Tau PET scan examines mid and superior temporal brain regions and the threshold is a Tau PET SUVR in the range of about 1.35 to about 1.45.

[0342] 155. The embodiment of any one of 151-154, wherein the Tau PET scan examines the lateral parietal brain region and the threshold is a Tau PET SUVR in the range of about 1.10 to about 1.45.

[0343] 156. The embodiment of any one of 151-155, further comprising determining that the patient is amyloid positive, wherein the patient is determined to be amyloid positive if the tau PET scan is above a certain threshold.

[0344] 157. A method of treating Alzheimer's disease in a patient identified as amyloid positive comprising administering an Alzheimer's treatment, wherein the patient is identified as amyloid positive based on a tau PET scan.

[0345] 158. The embodiment of paragraph 157, wherein the Tau PET scan examines the inferior temporal brain region and the Tau PET scan identifies the patient if the Tau PET SUVR is 1.45.

[0346] 159. The embodiment of any one of 157-158, wherein the Tau PET scan examines the lateral temporal brain region and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0347] 160. The embodiment of any one of 157-159, wherein the Tau PET scan examines mid and upper temporal brain regions and areas, and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0348] 161. The embodiment of any one of 157-160, wherein the Tau PET scan examines lateral parietal brain regions and regions, and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0349] 162. The embodiments of any one of 157-161, further comprising the treatment for Alzheimer's selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0350] 163. A method of treating Alzheimer's disease in a patient identified as being at risk for Alzheimer's cognitive decline comprising administering an Alzheimer's treatment, wherein the patient is identified as being at risk for Alzheimer's cognitive decline based on a tau PET scan.

[0351] 164. The embodiment of claim 163, wherein the Tau PET scan examines the inferior temporal brain region and the Tau PET scan identifies the patient if the Tau PET SUVR is 1.45.

[0352] 165. The embodiment of any one of 163-164, wherein the Tau PET scan examines the lateral temporal brain region and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0353] 166. The embodiment of any one of 163-165, wherein the Tau PET scan examines mid- and upper-temporal brain regions and areas, and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0354] 167. The embodiment of any one of 163-166, wherein the Tau PET scan examines lateral parietal brain regions and regions, and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0355] 168. The embodiment of any one of 163-167, further comprising determining that the patient is amyloid positive, wherein the patient is determined to be amyloid positive if the tau PET scan is above a certain threshold.

[0356] 169. The embodiments of any one of 163-168, further comprising the treatment for Alzheimer's selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab.

[0357] 170. A method of treating Alzheimer's disease in a patient identified as amyloid positive and at risk for Alzheimer's cognitive decline comprising administering an Alzheimer's treatment, wherein the patient is identified as amyloid positive and at risk for Alzheimer's cognitive decline based on a tau PET scan.

[0358] 171. The embodiment of claim 170, wherein the Tau PET scan examines the inferior temporal brain region and the Tau PET scan identifies the patient if the Tau PET SUVR is 1.45.

[0359] 172. The embodiment of any one of 170-171, wherein the Tau PET scan examines the lateral temporal brain region and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0360] 173. The embodiment of any one of 170-172, wherein the Tau PET scan examines mid and upper temporal brain regions and areas, and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.35 to about 1.45.

[0361] 174. The embodiment of any one of 170-173, wherein the Tau PET scan examines lateral parietal brain regions and regions, and the Tau PET scan identifies the patient if the Tau PET SUVR is in the range of about 1.10 to about 1.45.

[0362] 175. Further, the treatment for Alzheimer's is selected from donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, and lecanemab, any one of 170 to 174.

[0363] 176. The embodiment of any one of 157-162, wherein the patient is further identified as being at risk for Alzheimer's cognitive decline based on a tau PET scan.

[0364] In view of the above, it will be seen that the advantages of the disclosure are attained and other advantageous results obtained. Since various changes may be made in the methods described above without departing from the scope of the disclosure, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

[0365] When introducing elements of this disclosure or various versions, embodiments or aspects thereof, the articles "a," "an," "the," and "said" are intended to mean that there are one or more elements. The terms "comprising," "including," and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

Claims

1. 1. A method of identifying a patient suffering from or suspected of suffering from Alzheimer's disease as a candidate patient for receiving Alzheimer's disease treatment, comprising: analyzing a tau positron emission tomography (PET) scan of a brain region of the patient to determine a tau PET SUVR; and identifying the patient as a candidate patient for receiving Alzheimer's disease treatment if the tau PET SUVR is in the range of about 1.05 to about 1.

45.

2. The method of claim 1 , wherein the brain region is the inferior temporal brain region.

3. 3. The method of claim 1 or 2, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR ranges from about 1.35 to about 1.

45.

4. 4. The method of any one of claims 1 to 3, wherein said brain regions are the middle and superior temporal brain regions and said Tau PET SUVR ranges from about 1.35 to about 1.

45.

5. 5. The method of any one of claims 1 to 4, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR ranges from about 1.10 to about 1.

45.

6. 6. The method of any one of claims 1 to 5, wherein said brain regions are bilateral entorhinal cortex brain regions and said Tau PET SUVR ranges from about 1.05 to about 1.

45.

7. 7. The method of any one of claims 1-6, wherein the brain region is the fusiform gyrus brain region and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

8. 8. The method of any one of claims 1 to 7, wherein the brain region is the parahippocampal brain region and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

9. 9. The method of any one of claims 1 to 8, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is about 1.

45.

10. 10. The method of any one of claims 1 to 9, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

11. The method of any one of claims 1 to 10, further comprising determining a cortical thickness.

12. The method of any one of claims 1 to 11, further comprising analyzing cerebrospinal fluid for amyloid beta.

13. The method of any one of claims 1 to 12, further comprising analyzing the ε4 allele of apolipoprotein E (APOE ε4) genotype.

14. The method of any one of claims 1 to 13, wherein the patient is identified as having amyloid plaques and / or at risk of developing amyloid plaques based on the Tau PET SUVR.

15. 15. The method of any one of claims 1-14, wherein the patient is identified as at risk of having Alzheimer's disease cognitive decline based on the Tau PET SUVR.

16. 16. The method of any one of claims 1 to 15, further comprising administering to the patient an Alzheimer's disease therapy.

17. 1. A method of treating a patient suffering from or suspected of suffering from Alzheimer's disease, comprising: analyzing a tau PET scan of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.05 to about 1.

45.

18. 1. A method of treating a patient identified or determined to have amyloid plaques, comprising: analyzing tau images of a brain region of the patient to determine a tau PET SUVR; and administering an Alzheimer's disease treatment to the patient if the tau PET SUVR is in the range of about 1.05 to about 1.

45.

19. 19. The method of any one of claims 16 to 18, wherein the Alzheimer's disease treatment is donanemab, LY3372689, N3pG IV or LY3372993, ADUHELM®, solanezumab, gantenerumab, or lecanemab.

20. 19. The method of any one of claims 16-18, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

21. 21. The method of any one of claims 16-20, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR ranges from about 1.35 to about 1.

45.

22. 22. The method of any one of claims 16-21, wherein the brain regions are the middle and superior temporal brain regions and the Tau PET SUVR ranges from about 1.35 to about 1.

45.

23. 23. The method of any one of claims 16-22, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR ranges from about 1.10 to about 1.

45.

24. 24. The method of any one of claims 16-23, wherein the brain regions are bilateral entorhinal cortex brain regions and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

25. 25. The method of any one of claims 16-24, wherein the brain region is the fusiform brain region and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

26. 26. The method of any one of claims 16-25, wherein the brain region is the parahippocampal brain region and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

27. 27. The method of any one of claims 16 to 26, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is about 1.

45.

28. 28. The method of any one of claims 16 to 27, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

29. The method of any one of claims 16 to 28, further comprising determining cortical thickness.

30. 30. The method of any one of claims 16 to 29, further comprising analyzing cerebrospinal fluid for amyloid beta.

31. The method of any one of claims 16 to 30, further comprising analyzing the ε4 allele of apolipoprotein E (APOE ε4) genotype.

32. 32. The method of any one of claims 17-31, further comprising obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

33. 33. The method of any one of claims 17 or 19-32, further comprising identifying the patient as having amyloid plaques and / or at risk of developing amyloid plaques based on the Tau PET SUVR.

34. 34. The method of any one of claims 17 or 19-33, further comprising identifying the patient as at risk for having Alzheimer's disease cognitive decline based on the Tau PET SUVR.

35. 33. The method of any one of claims 17 to 32, wherein the patient is further identified as being at high risk of having Alzheimer's disease cognitive decline.

36. 36. The method of any one of claims 16-32 or 35, further comprising obtaining a tau positron emission tomography (PET) scan from the patient's brain region and analyzing the tau PET scan to determine a tau PET SUVR after administration of the Alzheimer's disease treatment.

37. 1. A method of diagnosing a patient as having or suspected of having Alzheimer's disease, comprising: analyzing a tau positron emission tomography (PET) scan of a brain region of the patient to determine a tau PET SUVR; and diagnosing the patient as having or suspected of having Alzheimer's disease if the tau PET SUVR is in the range of about 1.05 to about 1.

45.

38. 38. The method of claim 37, wherein the brain region is the inferior temporal brain region.

39. 39. The method of claim 37 or 38, wherein the brain region is the lateral temporal brain region and the Tau PET SUVR is in the range of about 1.35 to about 1.

45.

40. 40. The method of any one of claims 37-39, wherein said brain regions are the middle and superior temporal brain regions and said Tau PET SUVR ranges from about 1.35 to about 1.

45.

41. 41. The method of any one of claims 37-40, wherein the brain region is the lateral parietal brain region and the Tau PET SUVR ranges from about 1.10 to about 1.

45.

42. 42. The method of any one of claims 37-41, wherein the brain regions are bilateral entorhinal cortex brain regions and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

43. 43. The method of any one of claims 37-42, wherein the brain region is the fusiform gyrus brain region and the Tau PET SUVR ranges from about 1.05 to about 1.

45.

44. 44. The method of any one of claims 37-43, wherein the brain region is the parahippocampal brain region and the Tau PET SUVR is in the range of about 1.05 to about 1.

45.

45. 45. The method of any one of claims 37-44, wherein the brain region is the inferior temporal brain region and the Tau PET SUVR is about 1.

45.

46. 46. ​​The method of any one of claims 37 to 45, further comprising analyzing an amyloid positron emission tomography (PET) scan to determine amyloid status.

47. The method of any one of claims 37 to 46, further comprising determining cortical thickness.

48. 48. The method of any one of claims 37 to 47, further comprising analyzing cerebrospinal fluid for amyloid beta.

49. The method of any one of claims 37 to 48, further comprising analyzing the ε4 allele of apolipoprotein E (APOE ε4) genotype.

50. 50. The method of any one of claims 37-49, further comprising administering to the patient an Alzheimer's disease therapy if the Tau PET SUVR is in the range of about 1.10 to about 1.

45.

51. 51. The method of any one of claims 37-50, wherein the patient is identified as having amyloid plaques and / or at risk for developing amyloid plaques based on the Tau PET SUVR.

52. 52. The method of any one of claims 37-51, wherein the patient is identified as at risk for having Alzheimer's disease cognitive decline based on the Tau PET SUVR.

53. 53. The method of any one of claims 37 to 52, further comprising administering to the patient an Alzheimer's disease therapy.

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