An animal model (e.g., mouse) and method of use, and cell culture assay method, for characterizing or screening a test compound for its effect on late onset Alzheimer's disease (LOAD). The test compound may be used as a therapeutic agent for treatment of Alzheimer's disease (AD). The AD animal model may be haploinsufficient for Shugoshin 1 (Sgo1) gene, or may comprise a genetic modification enabling modulation of Sgo1 expression in the brain of the animal when exposed to an Sgo1 expression-modulating compound, such as tamoxifen. After the test compound is administered to the animal model, the presence or amount of an AD biomarker is assessed or measured.

The present disclosure provides immunodeficient mouse models that comprise a nucleic acid encoding a human or humanized amyloid precursor protein (APP) and, in some models, further comprise a nucleic acid encoding a mutated human presenilin 1 protein (PSEN1). These mouse models are useful, for example, for Alzheimer's disease studies.

Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models.

The present invention relates to a composition for the diagnosis of a degenerative brain disease, comprising hpmA, which is a substance derived from Proteus, Shigella, Klebsiella pneumoniae, or Citrobacter, preferably a Proteus mirabilis strain, from a biological sample of a subject. In addition, the present invention relates to a method for providing information for the diagnosis of a degenerative brain disease such as Parkinson's disease, brain neuritis (neuroinflammation), or Alzheimer's disease, by measuring the amount of hpmA.

Genetically modified mice characterized by one or more symptoms or signs associated with expression of human APOE4p and mouse Trem2p and relevant to non-familial late-onset Alzheimer's disease are provided wherein the genome of the mouse includes: 1) a DNA sequence encoding a human APOE4 protein (APOE4p) operably linked to a promoter; and 2) a DNA sequence encoding a mouse Trem2 protein having a mutation p,R47H (Trem2p) operably linked to a promoter, such that the mouse expresses human APOE4p and mouse Trem2p. Methods ace provided for screening for a compound for use in the treatment of Alzheimer's disease using such genetically modified mice.

The present invention relates to the development of and use of genetically modified human differentiated cells coupled with xenotransplantation into animal models to identify injury and disease-specific RNA and/or protein biomarkers. Specifically, the present invention encompasses two complementary methods for biomarker discovery that enable the direct and selective labelling, isolation, and analysis of human-specific RNA and/or proteins from xenotransplantation (or chimeric) animal models. Both methods involve the treatment of animal models with an RNA analog and/or amino acid analog that enables the specific isolation and quantification of human RNAs and/or proteins for the identification of novel human biomarkers for a large array of human injuries and diseases.

Described herein are compositions and methods for treating Alzheimer's disease or dementia. The compositions include mammalian suppressor of taupathy 2 inhibitors (MSUT2). The MSUT2 inhibitors can be small interfering RNAs, guide RNAs, or small molecules. The methods include reducing accumulation of phosphorylated and aggregated human tau.

This invention is directed to methods and compositions for increasing the expression or activity of neprilysin in, for example, the frontal cortex or the entorhinal cortex using a progranulin polypeptide or effector. The present invention is further directed to methods of reducing microglia in the brain of a patient with neurodegenerative disease using a progranulin polypeptide or effector.

Described herein are compositions and methods targeting IL-3 signaling for reducing Alzheimer's disease (AD)-related pathology.

The present disclosure is related to compositions that include polynucleotides encoding chimeric receptors, methods of delivering polynucleotides encoding chimeric receptors to immune cells, and methods of using immune cells encoding chimeric receptors to treat or prevent a neurological disease, disorder, or injury.