The present invention relates to novel compounds of the formula (I) ##STR00001##
that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.

The present disclosure provides monoclonal antibodies that bind -Synuclein. In certain aspects, the antibodies preferentially bind to -Synuclein fibrils over -Synuclein monomer. In other aspects, the invention comprises a method of treating -Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting -Synuclein fibrils using any of the antibodies of the invention.

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.

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.

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 provides antibodies that specifically bind to transthyretin (TTR). The antibodies can be used for treating or effecting prophylaxis of diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis). The antibodies can also be used for diagnosing TTR amyloidosis and inhibiting or reducing aggregation of TTR, among other applications.

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.

Methods are disclosed for determining whether a subject has a synucleinopathy. Methods are also disclosed for detecting misfolded alpha synuclein (Syn) in a biological sample or fraction thereof. These methods include the use of an Syn seeding assay.

A human antibody which comprises a complementarity determining region of an H chain consisting of the amino acid sequence as shown in SEQ ID NOs: 1 to 3 and a complementarity determining region of an L chain consisting of the amino acid sequence as shown in SEQ ID NOs: 4 to 6. The human antibody of the present invention has the activity to specifically bind to transthyretin (TTR) with structural change and the activity to inhibit fibrillization of TTR and is a human antibody suitable for application to human body.

In alternative embodiments, provided are compositions such as antibodies, e.g., single chain antibodies, that target 3-repeat (3R) Tau for the treatment of neurodegenerative disorders and taupathies such as Alzheimer's Disease (AD), Pick's Disease (PiD) and Fronto-temporal lobar degeneration (FTLD), or any disorder or condition associated with a 3R Tau accumulation, and methods for making and using them. In alternative embodiments, provided are brain-penetrating antibodies that specifically recognize 3R Tau, and methods of using them to treat, ameliorate, prevent or decrease the symptoms of neurodegenerative disorders including taupathies such as Alzheimer's Disease (AD), Pick's Disease (PiD) and Fronto-temporal lobar degeneration (FTLD), or any disorder or condition associated with a 3R Tau accumulation. Provided are methods for diagnosing a neurodegenerative disorder or a taupathy or any disorder or condition associated with a 3R Tau accumulation, and optionally the taupathy is Alzheimer's Disease, Pick's Disease or Fronto-temporal lobar degeneration.