biostudies-literatureAndo KBelgian Fonds de la Recherche Scientifique MédicaleFund Aline (King Baudouin Foundation)Foundation for Alzheimer Research (FRA/SAO)Génicot Fund of ULB3994https://www.ebi.ac.uk/biostudies/studies/S-EPMC9776874biostudies-literatureUnknown11(24)Genome-wide association studies (GWAS) have identified the <i>PICALM</i> (Phosphatidylinositol binding clathrin-assembly protein) gene as the most significant genetic susceptibility locus after <i>APOE</i> and <i>BIN1</i>. PICALM is a clathrin-adaptor protein that plays a critical role in clathrin-mediated endocytosis and autophagy. Since the effects of genetic variants of <i>PICALM</i> as AD-susceptibility loci have been confirmed by independent genetic studies in several distinct cohorts, there has been a number of in vitro and in vivo studies attempting to elucidate the underlying mechanism by which PICALM modulates AD risk. While differential modulation of APP processing and Aβ transcytosis by PICALM has been reported, significant effects of PICALM modulation of tau pathology progressiCellsPICALM and Alzheimer's Disease: An Update and Perspectives.PMC9776874140012019/00272021/0028Brion JPLeroy KLopez Gutierrez LNagaraj SAndo Kde Fisenne MADoeraene EKucukali FKosa ACfalsePICALM and Alzheimer's Disease: An Update and Perspectives.Genome-wide association studies (GWAS) have identified the <i>PICALM</i> (Phosphatidylinositol binding clathrin-assembly protein) gene as the most significant genetic susceptibility locus after <i>APOE</i> and <i>BIN1</i>. PICALM is a clathrin-adaptor protein that plays a critical role in clathrin-mediated endocytosis and autophagy. Since the effects of genetic variants of <i>PICALM</i> as AD-susceptibility loci have been confirmed by independent genetic studies in several distinct cohorts, there has been a number of in vitro and in vivo studies attempting to elucidate the underlying mechanism by which PICALM modulates AD risk. While differential modulation of APP processing and Aβ transcytosis by PICALM has been reported, significant effects of PICALM modulation of tau pathology progressi2022-01-01T00:00:00Z2022 Dec2026-04-08T18:18:07.829Z2025-04-04T18:52:36.365ZS-EPMC97768743655275610.3390/cells11243994