Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease.
Alzheimer disease (AD) is a neurodegenerative disease characterized by the extensive deposition of senile plaques and neurofibrillary tangles. Until recently, only theAPOEgene had been known as a genetic risk factor for late-onset AD (LOAD), which accounts for more than 95% of all AD cases. However, in addition to this well-established genetic risk factor, genome-wide association studies have identified several single nucleotide polymorphisms as genetic risk factors of LOAD, such asPICALMandBIN1. In addition, whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, includingTREM2. We review the recent findings related to the molecular mechanisms by which these genetic risk factors contribute to AD, and our perspectives regarding the etiology of AD for the development of therapeutic agents.
Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo.
Kunihiko
K
Kanatsu
Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, taisuke@mol.f.u-tokyo.ac.jp.
Taisuke
T
Tomita
D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011971:Receptors, Immunologic / Q000235:genetics; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human