1. APOE is linked to Alzheimer's disease in a large pedigree.
- Author
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Cai X, Fallin D, Stanton J, Scibelli P, Duara R, Crawford F, and Mullan M
- Subjects
- Age of Onset, Aged, Alleles, Alzheimer Disease epidemiology, Apolipoprotein C-I, Apolipoprotein E4, Apolipoproteins C genetics, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 14 genetics, Chromosomes, Human, Pair 19 genetics, Chromosomes, Human, Pair 21 genetics, DNA genetics, Female, Georgia epidemiology, Humans, Lod Score, Male, Middle Aged, Pedigree, Predictive Value of Tests, Recombination, Genetic, Alzheimer Disease genetics, Apolipoproteins E genetics
- Abstract
Although previous association studies have demonstrated that the APOE4 allele is a risk factor for Alzheimer's disease (AD), its value for the prediction of AD in individuals is <100%. The limited predictive value of epsilon4 is also seen in multiply affected families where the epsilon4 allele is not tightly linked to AD. We analyzed a large pedigree multiply affected with AD by lod score linkage analysis at the known loci associated with AD. In this pedigree, the APOE/APOCI gene area was linked to the development of AD, while no linkage was detected to any of the other loci known to be associated with the disease. In this family, then, the inheritance of an epsilon4 allele is highly associated with the early development of the disease (mean age of onset, 62 years), and is a good predictor of disease. However, given the wealth of evidence for association, but not linkage, of APOE4 to AD, we believe this finding suggests that another factor (or factors) interact(s) with APOE to precipitate early disease, and produce positive linkage results. The nature of this factor presently remains unknown.
- Published
- 1997