title: Alzheimer's disease risk genes and mechanisms of disease pathogenesis.
abstract: We review the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in AD pathogenesis. More recent advances in understanding of the human genome-technologic advances in methods to analyze millions of polymorphisms in thousands of subjects-have revealed new genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4-RIN3, SORL1, and ZCWPW1. Emerging technologies to analyze the entire genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2. We review the relationship between these AD risk genes and the cellular and neuropathologic features of AD. Understanding the mechanisms underlying the association of these genes with risk for disease will provide the most meaningful targets for therapeutic development to date.
authors.affiliation: Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Karch
authors.affiliation: Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri. Electronic address: goatea@psychiatry.wustl.edu.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D004705:Endocytosis; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D010641:Phenotype; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics; D012307:Risk Factors
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D002784:Cholesterol
keywords: Alzheimer’s Disease; Amyloid Precursor Protein; Cholesterol Metabolism; Endocytosis; Genome-Wide Association Studies; Immune Response