PICALM and Alzheimer's Disease: An Update and Perspectives

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 24; p. 3994
• Main Authors: Ando, Kunie, Nagaraj, Siranjeevi, Küçükali, Fahri, de Fisenne, Marie-Ange, Kosa, Andreea-Claudia, Doeraene, Emilie, Lopez Gutierrez, Lidia, Brion, Jean-Pierre, Leroy, Karelle
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2022; MDPI
• Subjects: Age; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Amino acids; amyloid β; Apolipoprotein E; Autophagy; Binding proteins; Biosynthesis; Bone marrow; Brain; Cholesterol; Chromosomes; Clathrin; Clathrin - metabolism; Development and progression; Endocytosis; Fibroblasts; Genes; Genetic diversity; Genetic Loci; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; GWAS; Health aspects; Health risk assessment; Homeostasis; Humans; Leukemia; microglia; Monomeric Clathrin Assembly Proteins - genetics; Monomeric Clathrin Assembly Proteins - metabolism; Mutation; Neurodegenerative diseases; neurofibrillary tangles; Neuropathology; Pathogenesis; Pathology; Peptides; Phosphatidylinositol; PICALM; Post-translation; Proteins; Review; Susceptibility; Tau protein; Belgium; GWAS; Alzheimer’s disease; amyloid β; microglia; neurofibrillary tangles; PICALM
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11243994

Genome-wide association studies (GWAS) have identified the (Phosphatidylinositol binding clathrin-assembly protein) gene as the most significant genetic susceptibility locus after and . PICALM is a clathrin-adaptor protein that plays a critical role in clathrin-mediated endocytosis and autophagy. Since the effects of genetic variants of 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 progression have also been evidenced in Alzheimer's disease models. In this review, we summarize the current knowledge about PICALM, its physiological functions, genetic variants, post-translational modifications and relevance to AD pathogenesis.