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

M. A. Pericak-Vance, C. C. Johnson, J. B. Rimmler, A. M. Saunders, L. C. Robinson, E. G. D'Hondt, C. E. Jackson, J. L. Haines

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)700-704
Number of pages5
JournalAnnals of neurology
Volume39
Issue number6
DOIs
StatePublished - Jun 1996
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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