Composition and method for preventing or treating a tauopathy
The present invention is a composition and method for the prevention and treatment of a tauopathy. The composition of the invention includes N-terminal amino acid residues of the tau protein, which have been identified as being involved in toxic activation of a PP1/GSK3 signaling cascade and inhibition of fast axonal transport in human tauopathies.
1. An isolated monoclonal antibody, or antigen binding antibody fragment thereof, raised against a tau peptide consisting of SEQ ID NO:1 or a peptide fragment thereof, wherein said antibody or antigen binding antibody fragment binds the tau peptide consisting of SEQ ID NO:1 and does not bind wild-type, non-denatured, soluble tau monomer.
2. The isolated antibody or antigen binding antibody fragment of claim 1 , wherein the tau peptide or peptide fragment is not post-translationally modified.
3. The isolated antibody or antigen binding antibody fragment of claim 1 , wherein the peptide fragment is between 5 and 16 amino acid residues in length.
4. The isolated antibody or antigen binding antibody fragment of claim 1 , wherein the antibody or antigen binding antibody fragment:
(a) binds tau paired helical filaments,
(b) binds denatured tau, or
(c) binds pathogenic tau from the brain of a patient with Alzheimer's disease.
5. A pharmaceutical composition comprising the isolated antibody or antigen binding antibody fragment of claim 1 and a pharmaceutically acceptable carrier.
6. A method for treating a tauopathy comprising administering to a subject with a tauopathy the pharmaceutical composition of claim 5 thereby treating the subject's tauopathy.
7. The method of claim 6 , wherein the tauopathy comprises Alzheimer's disease, progressive supranuclear palsy, frontotemporal dementia, Pick's disease, corticobasal degeneration, or post-encephalitic parkinsonism.