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Curr Psychiatry Rep. 2000 Apr;2(2):158-64.

The genetics of Alzheimer's disease.

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  • 1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Avenue, Seattle, WA 98108-1597, USA.


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.

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