# US 9,040,521 B2 · Methods and compositions for modulating tau levels > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,521 B2 - Document ID: US9040521B2 - Status: Granted - Kind: B2 - Application number: 13/502,659 - Filed: 2010-09-15 - Published: 2012-09-06 - Granted: 2015-05-26 - Earliest claimed: 2009-11-06 - Assignees: The J. David Gladstone Institutes - Applicants: Li Gan - Inventors: Li Gan - Web page: https://patentgrep.com/patent/US9040521B2 ## CPC - A61K 31/713: Double-stranded nucleic acids or oligonucleotides - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 31/4155: non condensed and containing further heterocyclic rings - A61K 31/551: having two nitrogen atoms, e.g. dilazep - A61K 38/50: acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease} - G01N 33/556: Fixed or stabilised red blood cell - G01N 2800/2814: Dementia; Cognitive disorders - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Methods and agents for reducing a level of an acetylated Tau polypeptide in a cell are provided. Methods for treating a tauopathy in an individual are also provided. Also provided is a method for diagnosing a cognitive impairment disorder in an individual. Methods for identifying an agent suitable for treating a tauopathy are also provided. ## Claims ### Claim 1 A method for reducing the level of an acetylated Tau polypeptide in a cell, the method comprising contacting the cell with an agent that increases the activity of a polypeptide that deacetylates a Tau polypeptide in the cell and/or an agent that decreases the activity of a polypeptide that acetylates a Tau polypeptide in the cell. ### Claim 2 (depends on 1) The method of claim 1, wherein the method comprises contacting the cell with an agent that increases the activity of a polypeptide that deacetylates a Tau polypeptide in the cell and an agent that decreases the activity of a polypeptide that acetylates a Tau polypeptide in the cell. ### Claim 3 (depends on 1) The method of claim 1, wherein the cell is a neuron. ### Claim 4 (depends on 1) The method of claim 1, wherein the cell is a glial cell. ### Claim 5 (depends on 1) The method of claim 1, wherein the agent is not a sirtuin activator. ### Claim 6 (depends on 1) The method of claim 1, wherein the agent is a p300 inhibitor or a CBP inhibitor. ### Claim 7 (depends on 1) The method of claim 1, wherein the agent is an activator of SIRT1, SIRT2, or HDAC6. ### Claim 8 (depends on 1) The method of claim 1, wherein said contacting reduces the level of phosphorylated Tau polypeptide in the cell. ### Claim 9 (depends on 1) The method of claim 1, wherein said contacting increases the level of active Tau polypeptide in the cell. ### Claim 10 A method for treating a tauopathy in an individual, the method comprising administering to the individual an effective amount of an agent that reduces the level of acetylated Tau in a neuron or a glial cell in the individual. ### Claim 11 (depends on 10) The method of claim 10, wherein the administering comprises administering to the individual an agent that increases the activity of a polypeptide that deacetylates a Tau polypeptide in a neuronal cell or a glial cell and an agent that decreases the activity of a polypeptide that acetylates a Tau polypeptide in a neuronal cell or a glial cell in combined effective amounts to treat the tauopathy. ### Claim 12 (depends on 10) The method of claim 10, wherein the tauopathy is frontotemporal dementia, Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, Down syndrome, dementia pugilistica, inclusion-body myositis, or frontotemporal lobar degeneration. ### Claim 13 (depends on 10) The method of claim 10, wherein the agent that reduces the level of acetylated Tau is a P300/CBP inhibitor. ### Claim 14 (depends on 10) The method of claim 10, wherein the agent that reduces the level of acetylated Tau is a SIRT1 activator. ### Claim 15 (depends on 10) The method of claim 10, wherein said administering reduces the level of phosphorylated Tau in a neuron or glial cell in the individual. ### Claim 16 (depends on 10) The method of claim 10, wherein said administering increases the level of active Tau in a neuron or glial cell in the individual. ### Claim 17 A method of diagnosing a cognitive impairment disorder in an individual, the method comprising detecting a level of acetylated Tau polypeptide in a biological sample obtained from the individual, wherein a level of acetylated Tau polypeptide that is higher than a normal control level indicates that the individual has a cognitive impairment disorder. ### Claim 18 (depends on 17) The method of claim 17, wherein the biological sample is cerebrospinal fluid, blood, plasma, or serum.