The genetics of Alzheimer's disease.
Alzheimer's disease (AD) is a genetically complex disorder. Mutations in the amyloid precursor protein and presenilin 1 (PS1) genes are fully penetrant and cause early-onset AD. Mutations in presenilin 2, a PS1 homologue, cause partially penetrant autosomal dominant AD with onset age beginning at 40 years and extending past 75 years. A fourth gene, apolipoprotein E (ApoE) is a risk-factor for late-onset AD. Over 40 genes have been tested as AD candidate genes, yet none has been clearly established as an AD risk factor. Linkage studies have implicated a number of chromosome regions as possible sites for late-onset AD loci with the strongest evidence being for chromosome 12. Candidate genes in this region include alpha2-macroglobulin (A2M) and low-density lipoprotein receptor-related gene (LRP), although neither has been clearly established as an AD gene. Identification of additional late-onset genes will require larger samples, more sophisticated analysis methods, and large-scale positional cloning efforts.
Schellenberg
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Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Avenue, Seattle, WA 98108-1597, USA. Zachdad@U.Washington.edu
D'Souza
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Poorkaj
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D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D053764:Presenilin-1; D053766:Presenilin-2; D000511:alpha-Macroglobulins / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D005819:Genetic Markers; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D000511:alpha-Macroglobulins