Maternal lineages and Alzheimer disease risk in the Old Order Amish.

Journal Article (Journal Article)

Old Order Amish, founded by a small number of Swiss immigrants, exist in culturally isolated communities across rural North America. The consequences of genetic isolation and inbreeding within this group are evident by increased frequencies of many monogenic diseases and several complex disorders. Conversely, the prevalence of Alzheimer disease (AD), the most common form of dementia, is lower in the Amish than in the general American population. Since mitochondrial dysfunction has been proposed as an underlying cause of AD and a specific haplogroup was found to affect AD susceptibility in Caucasians, we investigated whether inherited mitochondrial haplogroups affect risk of developing AD dementia in Ohio and Indiana Amish communities. Ninety-five independent matrilines were observed across six large pedigrees and three small pedigrees then classified into seven major European haplogroups. Haplogroup T is the most frequent haplogroup represented overall in these maternal lines (35.4%) while observed in only 10.6% in outbred American and European populations. Furthermore, haplogroups J and K are less frequent (1.0%) than in the outbred data set (9.4-11.2%). Affected case matrilines and unaffected control lines were chosen from pedigrees to test whether specific haplogroups and their defining SNPs confer risk of AD. We did not observe frequency differences between AD cases compared to controls overall or when stratified by sex. Therefore, we suggest that the genetic effect responsible for AD dementia in the affected Amish pedigrees is unlikely to be of mitochondrial origin and may be caused by nuclear genetic factors.

Full Text

Duke Authors

Cited Authors

  • van der Walt, JM; Scott, WK; Slifer, S; Gaskell, PC; Martin, ER; Welsh-Bohmer, K; Creason, M; Crunk, A; Fuzzell, D; McFarland, L; Kroner, CC; Jackson, CE; Haines, JL; Pericak-Vance, MA

Published Date

  • October 2005

Published In

Volume / Issue

  • 118 / 1

Start / End Page

  • 115 - 122

PubMed ID

  • 16078048

International Standard Serial Number (ISSN)

  • 0340-6717

Digital Object Identifier (DOI)

  • 10.1007/s00439-005-0032-x


  • eng

Conference Location

  • Germany