BIN1 as a risk factor in late-onset Alzheimer's disease

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A major focus of our current research is to understand how the second most common late-onset Alzheimer's disease risk gene, namely BIN1, contributes to disease pathophysiology. BIN1 is a member of the BAR (Bin/Amphiphysin/ Rvs) adaptor family proteins that regulate membrane dynamics in a variety of cellular contexts, including endocytosis and membrane remodeling. The BIN1 gene undergoes complex alternative splicing to generate more than 15 isoforms, which differ in their tissue distribution, subcellular localization, and function. The challenge is to characterize the neuronal and non-neuronal BIN1 expression and investigate, using a series of conditional knock-out and transgenic mouse models, how BIN1 elevates the risk for AD . Our characterization of neuronal Bin1 cKO mice revealed that BIN1 regulates presynaptic neurotransmitter release and memory consolidation -

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Andrew RJ et al.   Reduction of late-onset Alzheimer’s disease risk-factor BIN1 expression does not affect amyloid pathology in a mouse model of Alzheimer’s disease. J. Biol. Chem. 2019. 294(12):4477-4487.

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De Rossi P et al.  Aberrant accrual of BIN1 near Alzheimer’s disease amyloid deposits in transgenic models. Brain Pathology, 2018. doi: 10.1111/bpa.12687.  Full Text

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De Rossi P et al.  BIN1 localization is distinct from Tau tangles in Alzheimer’s disease. Matters, 2017. Full Text

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De Rossi P et al.  Predominant expression of Alzheimer's disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts. Mol. Neurodegener. 2016, 11:59. DOI 10.1186/s13024-016-0124-1. Full Text