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The genetics of Alzheimer’s disease

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Abstract

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 riskfactor 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 regioninclude α2-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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Schellenberg, G.D., D’Souza, I. & Poorkaj, P. The genetics of Alzheimer’s disease. Curr Psychiatry Rep 2, 158–164 (2000). https://doi.org/10.1007/s11920-000-0061-z

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