Alzheimer's disease and apolipoprotein E-4 allele in an Amish population.

Published

Journal Article

Alzheimer's Disease (AD) is a complex genetic disorder with four loci already identified. Mutations in three of these, the amyloid precursor protein, presenilin I, and presenilin II, cause early-onset AD. The apolipoprotein E (APOE) gene contributes primarily to late-onset AD. The APOE-4 allele acts in a dose-related fashion to increase risk and decrease the age-of-onset distribution in AD. We examined the effect of APOE on AD in a previously unstudied Amish population that has a lower prevalence of dementia compared with other populations. We sampled a large inbred family with 6 late-onset AD members. We also genotyped 53 individuals from the general Amish population as controls for the APOE allele frequency estimates. The frequency of the APOE-4 allele in the Amish controls was 0.037 +/- 0.02. This differed significantly compared with three independent sets of non-Amish white controls (p < 2 x 10(-4), p < 6 x 10(-5), and p < 2 x 10(-6)). In addition, all Amish AD-affected individuals had APOE 3/3 genotypes; no APOE X/4 or 4/4 individuals were observed. We suggest that the lower frequency of dementia in the Amish may be partially explained by the decreased frequency of the APOE-4 allele in this population, and that the inbred nature of this pedigree, with its strong clustering of cases contrasted against the lower frequency of dementia, indicates that additional genetic factors influence late-onset AD.

Full Text

Duke Authors

Cited Authors

  • Pericak-Vance, MA; Johnson, CC; Rimmler, JB; Saunders, AM; Robinson, LC; D'Hondt, EG; Jackson, CE; Haines, JL

Published Date

  • June 1996

Published In

Volume / Issue

  • 39 / 6

Start / End Page

  • 700 - 704

PubMed ID

  • 8651641

Pubmed Central ID

  • 8651641

International Standard Serial Number (ISSN)

  • 0364-5134

Digital Object Identifier (DOI)

  • 10.1002/ana.410390605

Language

  • eng

Conference Location

  • United States