The present invention provides methods and compositions for expanding T regulatory cells ex vivo or in vivo using one or more SAP agonists. The methods and compositions are useful in the treatment of autoimmune diseases and in preventing foreign graft rejection.

The disclosure pertains to antibodies that bind A-beta oligomers and methods of making and using said antibodies.

A method inhibiting and/or reducing -amyloid accumulation and/or Tau aggregation in a subject in need thereof includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of the LAR family phosphatases.

The present invention relates to a cell therapy method for treating neurodegenerative diseases, which includes administering a therapeutically effective amount of a regulatory T cell to an individual in need thereof. The regulatory T cell may be an amyloid-beta specific regulatory T cell induced by administering amyloid-beta peptide and bee venom phospholipase A2 (bvPLA2).

Aggregated Tau protein is associated with over 20 neurological disorders including Alzheimer's disease. Previous work has shown that Tau's sequence segments VQIINK and VQIVYK drive its aggregation, and that inhibitors based on the structure of the VQIVYK segment partially inhibit Tau aggregation. Here we show that the VQIINK segment is the more powerful driver of Tau aggregation. Two structures of this segment determined by the cryo EM method MicroED explain its more powerful seeding. Of practical significance, the understanding of the structures has led to the design of structure based peptide inhibitors that effectively inhibit Tau aggregation as well as the ability of exogenous Tau fibrils to seed intracellular Tau in mammalian cells into amyloid.

The present invention relates to a method of treating or preventing a neurological condition mediated by a tau-dependent signalling complex in neurons of a subject, comprising treating the subject to: (a) promote phosphorylation of one or more amino acids residues of tau, wherein the phosphorylation of the amino acid residues causes disruption of the tau-dependent signalling complex in neurons of the subject; or (b) introduce a variant of tau that causes disruption of the tau-dependent signalling complex in neurons of the subject. The invention also relates to vectors, compositions and kits for treating or preventing a neurological condition mediated by a tau-dependent signalling complex in neurons of a subject.

The disclosure pertains to conformational epitopes in A-beta, antibodies thereto and methods of making and using immunogens and antibodies specific thereto.

Aspects of the present disclosure are directed to compositions and methods for treating a subject having a neurodegenerative disorder, disease, or condition. Certain aspects relate to treatment with a therapeutically effective amount of a composition comprising a vector encoding an A peptide variant. Further aspects relate to methods of inhibiting aggregation of endogenous A peptide in vivo by contacting at least one such peptide with a therapeutically effective amount of an expressed A peptide variant from a vector encoding the A peptide variant, said vector in a composition.

Detection, diagnosis, and monitoring of Alzheimer's disease can be achieved with antibody-based detection methods directed to detect at least two regions of the amyloid beta peptide. The invention recognizes and relies on the observation that the steric availability of the carboxyl terminal epitope and the amino terminal epitope in an amyloid beta peptide differs based on whether the amyloid beta is monomeric or oligomeric. Due to oligomerization, the measured concentration of carboxyl termini that are available for binding represents the amount of monomeric amyloid beta in the sample; whereas the measured concentration of amino termini that are available for binding represents total amyloid beta (i.e., monomeric plus oligomeric) in the sample. Comparing the relative binding therefore can be used to characterize the population of soluble amyloid beta oligomers in the sample. The measurements are useful for early detection and subsequent monitoring of the development of Alzheimer's disease in a patient.

Peptide analogues of ?-amyloid and methods of using said analogues for neuroprotection are described herein. The ?-amyloid peptide analogues have a sequence that is at least 50% identical to an N-terminal ?-amyloid core fragment. A pharmaceutical composition of the ?-amyloid peptide analogues in a pharmaceutically acceptable carrier can be administered to a subject for neuromodulation. The ?-amyloid peptide analogues, while lacking neurotoxicity, effectively provides for protective activity against ?-amyloid toxicity.