A method of detecting the presence of alpha-synuclein aggregation in a biological sample is provided whereby a biological sample is mixed with a reaction sample comprising a population of beads, a fluorophore adapted to bind to protein aggregates and to increase fluorescence when bound to protein aggregates, and alpha-synuclein or a fragment or variant thereof to form a reaction mixture, the reaction mixture is illuminated and at the same time incubated with intermittent agitation cycles, wherein a significant increase in the fluorescence of the reaction mixture during incubation is indicative of the presence of aggregates of alpha-synuclein in the biological sample. Method of diagnosing alpha-synucleinopathies such as Parkinson's disease or Dementia with Lewy Bodies.

A monoclonal antibody that binds α-synuclein, and that binds tau fibrils, and methods of using the monoclonal antibody, are provided. The monoclonal antibody may be hybridoma clone 2F11. Also provided is a composition comprising the monoclonal antibody 2F11 and a pharmaceutically acceptable carrier, adjuvant, vehicle or excipient. A method of reducing active α-synuclein in a subject in need thereof is also disclosed. The method involves administering an amount of the composition comprising 2F11 to the subject. The monoclonal antibody 2F11 may also be used to determine the α-synuclein, or tau fibril, level in a biological sample.

The invention relates to antibodies, antibody fragments and binding agents that specifically recognize oligomeric tau but do not bind to monomeric tau, fibrillar tau or non-disease associated forms of tau.

The present invention provides a model animal for establishing an effective therapy for a protein aggregation disease typified by Alzheimer's disease and the like.

More specifically, the present invention provides the followings: (A) a non-human animal that exhibits a degenerative symptom attributed to protein aggregation, wherein the degenerative symptom attributed to protein aggregation is induced by misfolding of the protein and said degenerative symptom is promoted; and (B) a method for producing the non-human animal that exhibits the degenerative symptom attributed to the protein aggregation, comprising the following (1) and (2): (1) inducing misfolding of the protein to cause the degenerative symptom attributed to the protein aggregation in the non-human animal, and (2) giving a treatment to promote the degenerative symptom attributed to the protein aggregation in the non-human animal.

Monoclonal anti-PHF-tau antibodies and antigen-binding fragments thereof are described. Also described are nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies and using the antibodies for treating or preventing conditions such as tauopathies.

The invention disclosed herein relates to peptide inhibitors for transthyretin (TTR) aggregation and methods of inhibiting TTR aggregation, cytotoxicity, and/or TTR amyloidosis. Illustrative embodiments of the invention include a composition of matter comprising at least one peptide designed to inhibit the aggregation of TTR, with this peptide typically being coupled to a heterologous amino acid tag. A pharmaceutically acceptable carrier selected to be compatible with the inhibitory peptide may also be included. A method for blocking or inhibiting the aggregation of transthyretin TTR is also provided. The method comprises combining TTR with an effective amount of an inhibitory peptide or pharmaceutical composition, so that TTR aggregation and/or cytotoxicity is blocked or inhibited.

Cas-protein-ready tau biosensor cells, CRISPR/Cas synergistic activation mediator (SAM)-ready tau biosensor cells, and methods of making and using such cells to screen for genetic modifiers of tau seeding or aggregation are provided. Reagents and methods for sensitizing such cells to tau seeding activity or tau aggregation or for causing tau aggregation are also provided.

The present disclosure relates to compounds, compositions, and methods for the inducing neurodegenerative disease pathologies. In one aspect, disclosed herein is a nucleotide sequence encoding a chimeric polypeptide, comprising: a first nucleotide sequence encoding a light-induced oligomerization domain and a second nucleotide sequence encoding a neurodegenerative disease in target protein. Disclosed herein is a method of inducing a neurodegenerative disease pathology in a cell, comprising the steps: introducing into the cell an expression vector encoding a chimeric polypeptide, comprising: a first nucleotide sequence encoding a light-induced oligomerization domain and a second nucleotide sequence encoding a low complexity domain from a neurodegenerative disease target protein, wherein the first nucleotide sequence is operably linked to a promoter; expressing the chimeric polypeptide; and inducing oligomerization of the chimeric polypeptide by stimulation with blue light.

A monoclonal antibody that binds α-synuclein, and that binds tau fibrils, and methods of using the monoclonal antibody, are provided. The monoclonal antibody may be hybridoma clone 2F11. Also provided is a composition comprising the monoclonal antibody 2F11 and a pharmaceutically acceptable carrier, adjuvant, vehicle or excipient. A method of reducing active α-synuclein in a subject in need thereof is also disclosed. The method involves administering an amount of the composition comprising 2F11 to the subject. The monoclonal antibody 2F11 may also be used to determine the α-synuclein, or tau fibril, level in a biological sample.

The present invention is in the fields of biochemistry, molecular biology, and Alzheimer's disease diagnosis, prevention, and treatment. Provided herein are humanized antibodies against human tau that are capable of discriminating between normal (healthy) and pathological (disease-associated) tau.