The invention provides an antibody or antigen binding fragments thereof that binds to 3pE Aβ and methods of making and using the antibody or antigen binding fragment thereof, including use for formulations, administration and kits. The antibody and antigen binding fragments thereof and methods disclosed are useful for diagnosis, prognosis and treatment of Alzheimer's disease or other β-amyloid-related diseases.

Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models. The present disclosure shows that age dependent accumulation of genomic lesions leads to the production of RNA molecules within neurons that mimic viruses and intrinsically activate innate immune signaling, which triggers neurodegeneration. This hypothesis is supported by the results shown herein elucidating the mechanism of neurodegeneration in two mouse lines that specifically express different isoforms of the human amyloid precursor protein (hAPP) gene, which is associated with Alzheimer's disease (AD), exclusively in olfactory sensory neurons (OSNs) in the nose.

Provided herein are methods, assays and compositions relating to the treatment of neurological diseases and disorders, particularly by modulating expression and/or activity of Bif-1.

Disclosed herein is a rodent and human behavioral test for evaluating visual dysfunctions associated with the retinal changes in Alzheimer disease progression. In one example, the inventors developed a maze that tests rodent's ability to identify (1) specific contrasts, (2) specific colors, (3) certain items in the visual field, and (4) other ‘non-typical’ peripheral and night vision functions associated with AD. For instance, the inventors developed a maze the tests the rodents ability to avoid certain colors or contrasts gradients. The maze may include certain rooms with specific visual markers (e.g., colors, contrasts, objects or other visual features) that also contain shock plates.

Disclosed is the use of genetic means or a related inhibitor to inhibit and down-regulate the amount of PI4KIIIα protein, RBO/EFR3/EFR3A/EFR3B membrane proteins, TTC7 protein and membrane protein complexes formed by said proteins, or related enzyme activity to promote Aβ secretion by neuronal cells, reduce Aβ accumulation within neurons, and thereby reduce AD model fruit fly and mouse nerve dysfunction.

A method for treating a progressive neurodegenerative disorder with bone marrow stem cells and a G-CSF receptor agonist.

The present invention relates to cPLA2e inducing agents and cPLA2e inducing agents for use as a medicament, particularly for use in the treatment of a cognitive disorder and/or disease associated with a cognitive disorder, for example dementia, and more specifically age-related dementia and/or Alzheimer's disease.

Certain embodiments are directed to marker peptides or marker peptide antibodies can be used in producing diagnostic kits or used in diagnostic methods for Alzheimer's disease. The antibodies and/or marker peptides can be used in immunohistochemical and biochemical methods for qualitative and quantitative analysis of marker peptide levels and/or localization in brain samples and CSF samples.

The invention involves a method for modulating leukocyte activity, comprising delivering to a leukocyte a vector containing nucleic acid molecule(s), whereby the leukocyte contains Cas9 and the vector expresses one or more RNAs to guide the Cas9 to introduce mutations in one or more target genetic loci in the leukocyte, thereby modulating expression of one or more genes expressed in the leukocyte. The invention also involves identifying genes associated with leukocyte responses and experimental modeling of aberrant leukocyte activation and diseases associated with leukocytes by introducing mutations into leukocytes. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate leukocyte associated diseases.

Disclosed are a composition and method for inhibiting tau protein accumulation, aggregation, or tangle, the composition containing neurons or glia having Nurr1 and/or Foxa2 genes introduced thereinto, wherein the composition and method can be utilized in the prevention or treatment of a cerebral nervous disease caused by tau protein accumulation, aggregation, or tangle formation.