Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses.
The genetic underpinnings of Alzheimer's disease (AD) remain largely elusive despite early successes in identifying three genes that cause early-onset familial AD (those that encode amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2)), and one genetic risk factor for late-onset AD (the gene that encodes apolipoprotein E (APOE)). A large number of studies that aimed to help uncover the remaining disease-related loci have been published in recent decades, collectively proposing or refuting the involvement of over 500 different gene candidates. Systematic meta-analyses of these studies currently highlight more than 20 loci that have modest but significant effects on AD risk. This Review discusses the putative pathogenetic roles and common biochemical pathways of some of the most genetically and biologically compelling of these potential AD risk factors.
Bertram
Lars
L
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, Massachusetts 02129, USA. bertram@helix.mgh.harvard.edu
Tanzi
Rudolph E
RE
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001923:Brain Chemistry / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015201:Meta-Analysis as Topic; D009154:Mutation / Q000235:genetics*; D053763:Presenilins / Q000235:genetics; D012307:Risk Factors
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D053763:Presenilins