top of page

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

Cover image_Moorthi Ponnusamy_09-15-22.tif

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 various cellular contexts, including endocytosis and membrane remodeling. The BIN1 gene undergoes complex alternative splicing to generate more than 15 isoforms, which differ in 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.                             Neuronal BIN1 also regulates tau pathogenesis in a region-specific manner.                           Moreover, we observed that microglial BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia.                        Ongoing research focuses on cell-type-specific  functions of BIN1 using conditional knock-out and transgenic models.

Cover image_Moorthi Ponnusamy_09-15-22.tif

Ponnusamy M et al. Loss of forebrain BIN1 attenuates hippocampal pathology and neuroinflammation in a tauopathy model. Brain. 2022 Sept 5;awac318. doi:10.1093/brain/awac318.



Sudwarts A et al. BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia. Mol Neurodegener. 2022 May 7;17(1):33. doi: 10.1186/s13024-022-00535-x.



De Rossi P et al. Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation. Cell Rep. 2020 Mar 10;30(10):3520-3535.e7. doi: 10.1016/j.celrep.2020.02.026.


Rob BIN1 Het JBC.jpg

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.

Full Text

BIN1 5XFAD Brain Pathology.jpg

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

BIN Tau Matters.png

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

BIN1 HuBrain Mol Neurodeg.png

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

bottom of page