biostudies-literatureAndrew RJHHS | National Institutes of HealthNIA NIH HHSIllinois Department of Public HealthBrightFocus FoundationCure Alzheimer&apos;s FundAlzheimer&apos;s AssociationHHS | NIH | National Institute on AgingNIH HHS4477-4487https://www.ebi.ac.uk/biostudies/studies/S-EPMC6433054biostudies-literatureUnknown294(12)Alzheimer's disease (AD) is pathologically characterized by the deposition of the β-amyloid (Aβ) peptide in senile plaques in the brain, leading to neuronal dysfunction and eventual decline in cognitive function. Genome-wide association studies have identified the <i>bridging integrator 1</i> (<i>BIN1</i>) gene within the second most significant susceptibility locus for late-onset AD. BIN1 is a member of the amphiphysin family of proteins and has reported roles in the generation of membrane curvature and endocytosis. Endocytic dysfunction is a pathological feature of AD, and endocytosis of the amyloid precursor protein is an important step in its subsequent cleavage by β-secretase (BACE1). <i>In vitro</i> evidence implicates BIN1 in endosomal sorting of BACE1 and Aβ generation in neurons, The Journal of biological chemistryReduction of the expression of the late-onset Alzheimer's disease (AD) risk-factor <i>BIN1</i> does not affect amyloid pathology in an AD mouse model.PMC643305483282004FRF1 AG054223AG056061AARF-17–50122816477S10 OD010649AG054223A2017366FRF1 AG056061S10OD010649Guerbette TAndrew RJRice RCWagner SLDe Rossi PThinakaran GRecupero AJNguyen PKowalski HRLaury-Kleintop LKrause SVfalseReduction of the expression of the late-onset Alzheimer's disease (AD) risk-factor <i>BIN1</i> does not affect amyloid pathology in an AD mouse model.Alzheimer's disease (AD) is pathologically characterized by the deposition of the β-amyloid (Aβ) peptide in senile plaques in the brain, leading to neuronal dysfunction and eventual decline in cognitive function. Genome-wide association studies have identified the <i>bridging integrator 1</i> (<i>BIN1</i>) gene within the second most significant susceptibility locus for late-onset AD. BIN1 is a member of the amphiphysin family of proteins and has reported roles in the generation of membrane curvature and endocytosis. Endocytic dysfunction is a pathological feature of AD, and endocytosis of the amyloid precursor protein is an important step in its subsequent cleavage by β-secretase (BACE1). <i>In vitro</i> evidence implicates BIN1 in endosomal sorting of BACE1 and Aβ generation in neurons, 2019-01-01T00:00:00Z2019 Mar2026-05-03T14:19:41.696Z2026-04-07T19:19:14.893ZS-EPMC64330543069219910.1074/jbc.RA118.00637910.1074/jbc.ra118.006379