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US 11,635,440 B2Granted
Methods of treating based on site-specific tau phosphorylation
AssigneeWashington University
InventorsNicolas Barthelemy, Randall Bateman, Eric McDade
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods to quantify tau phosphorylation at specific amino acid residues to predict time to onset of mild cognitive impairment due to Alzheimer's disease, stage Alzheimer's disease, guide treatment decisions, select subjects for clinical trials, and evaluate the clinical efficacy of certain therapeutic interventions.
Claims30
A method for selecting a therapeutic agent for a subject in need thereof, the method comprising
- (a) providing an isolated tau sample obtained from the subject and measuring, in the isolated tau sample, tau phosphorylation at T205 and T181, at T205 and T217, or at T205, T181, and T217;
- and
- (b) administering to the subject a therapeutic agent, wherein:
- (i) the isolated tau sample obtained from the subject contains tau phosphorylation at T181 and/or tau phosphorylation at T217 that significantly deviates from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and tau phosphorylation at T205 that does not significantly deviate from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and the therapeutic agent prevents amyloid deposition from increasing or reduces a subject's existing plaque load, or
- (ii) the isolated tau sample obtained from the subject contains tau phosphorylation at T181 and/or tau phosphorylation at T217 that significantly deviates from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and tau phosphorylation at T205 that significantly deviates from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and the therapeutic agent prevents amyloid deposition from increasing, or reduces a subject's existing plaque load, or prevents tau aggregation, or targets neurofibrillary tangles.
2 more elements
A method for selecting a therapeutic agent for a subject in need thereof, the method comprising
- (a) providing an isolated tau sample obtained from the subject and measuring, in the isolated tau sample, tau phosphorylation at:
- (i) T205, T181, and at least one site selected from the group consisting of T111, T153, S208, or T231, or
- (ii) T205, T217, and at least one site selected from the group consisting of T111, T153, S208, or T231;
- and
- (b) administering to the subject a therapeutic agent, wherein:
- (i) the isolated tau sample obtained from the subject contains tau phosphorylation at T181 and/or tau phosphorylation at T217 that significantly deviates from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and tau phosphorylation at T205 that does not significantly deviate from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and the therapeutic agent prevents amyloid deposition from increasing or reduces a subject's existing plaque load, or
- (ii) the isolated tau sample obtained from the subject contains tau phosphorylation at T181 and/or tau phosphorylation at T217 that significantly deviates from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and tau phosphorylation at T205 that significantly deviates from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and the therapeutic agent prevents amyloid deposition from increasing, or reduces a subject's existing plaque load, or prevents tau aggregation, or targets neurofibrillary tangles.
4 more elements
A method for selecting a therapeutic agent for a subject in need thereof, the method comprising
- (a) providing an isolated tau sample obtained from the subject and measuring, in the isolated tau sample, tau phosphorylation at T205, and at least one site selected from the group consisting of T217, T181, T111, T153, S208, or T231,
- (b) administering to the subject a therapeutic agent, wherein:
- (i) the isolated tau sample obtained from the subject contains tau phosphorylation at T205 that does not significantly deviate from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and the therapeutic agent prevents amyloid deposition from increasing or reduces a subject's existing plaque load, or
- (ii) the isolated tau sample obtained from the subject contains tau phosphorylation at T205 that significantly deviates from the mean of a control population without brain amyloid plaques as measured by PET imaging and/or Aβ42/40 measurement in CSF, and the therapeutic agent prevents amyloid deposition from increasing, or reduces a subject's existing plaque load, or prevents tau aggregation, or targets neurofibrillary tangles.
1 more element
Dependencies are inferred from the claim text.