Familial and Population-Based Studies of Apolipoprotein E and Alzheimer's Disease

The finding of an association between the epsilon 4 allele of the APOE locus and the early expression of late-onset Alzheimer's disease (AD) is robust. However, the estimates of the proportion of AD cases carrying one or more copies of the epsilon 4 allele vary dramatically between studies (hig...

Full description

Saved in:
Bibliographic Details
Published in:Annals of the New York Academy of Sciences 1996-12, Vol.802 (1), p.16-26
Main Authors: MULLAN, MICHAEL, SCIBELLI, PAUL, DUARA, RANJAN, FALLIN, DANIELLE, GOLD, MICHAEL, SCHINKA, JOHN, HOYNE, JONATHAN, OSBORNE, AARON, SEVUSH, STEVEN, CRAWFORD, FIONA
Format: Article
Language:English
Subjects:
Age of Onset
Alleles
Alzheimer Disease - epidemiology
Alzheimer Disease - genetics
Apolipoprotein E4
Apolipoproteins E - genetics
Family
Florida
Gene Frequency
Genotype
Humans
Nuclear Family
Odds Ratio
Risk Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The finding of an association between the epsilon 4 allele of the APOE locus and the early expression of late-onset Alzheimer's disease (AD) is robust. However, the estimates of the proportion of AD cases carrying one or more copies of the epsilon 4 allele vary dramatically between studies (highest estimates being 180% of lowest ones). Here we compare the results of association studies in samples drawn from an epidemiologically based study design and samples drawn from families selected for linkage studies. The significant differences between results probably point to the unwitting selection of familial factors other than the APOE locus in the family history positive samples. We conclude that any selection procedure tending to enrich samples for positive family history will also tend to artificially increase APOE epsilon 4 allele frequencies in probands. This is of significance in samples drawn from clinical settings where referral may be influenced by previous known family history. Further work is needed to clarify the nature of the additional factors operating within families. We also report data showing an association between late-onset AD and a polymorphism in an adjacent locus to APOE-the APOCI locus. As no additional risk for AD can be attributed to the APOCI locus, the most likely explanation for the association between AD and APOCI is the disequilibrium between the APOCI and APOE loci. Therefore, there are likely to be other genetic markers in the area that can be used in the same way as APOE as a marker of risk for the disease.
ISSN:0077-8923
1749-6632
DOI:10.1111/j.1749-6632.1996.tb32594.x