PICALM and Alzheimer’s Disease: An Update and Perspectives
Kunie Ando,
Siranjeevi Nagaraj,
Fahri Küçükali,
Marie-Ange de Fisenne,
Andreea-Claudia Kosa,
Emilie Doeraene,
Lidia Lopez Gutierrez,
Jean-Pierre Brion,
Karelle Leroy
Affiliations
Kunie Ando
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Siranjeevi Nagaraj
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Fahri Küçükali
Complex Genetics of Alzheimer’s Disease Group, VIB Center for Molecular Neurology, VIB Antwerp, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium
Marie-Ange de Fisenne
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Andreea-Claudia Kosa
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Emilie Doeraene
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Lidia Lopez Gutierrez
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Jean-Pierre Brion
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Karelle Leroy
Laboratory of Histology, Neuropathology and Neuroanatomy, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, 808 Route de Lennik, 1070 Brussels, Belgium
Genome-wide association studies (GWAS) have identified the PICALM (Phosphatidylinositol binding clathrin-assembly protein) gene as the most significant genetic susceptibility locus after APOE and BIN1. PICALM is a clathrin-adaptor protein that plays a critical role in clathrin-mediated endocytosis and autophagy. Since the effects of genetic variants of PICALM 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.
