Familial and population-based studies of apolipoprotein E and Alzheimer's disease

Michael Mullan, Paul Scibelli, Ranjan Duara, Danielle Fallin, Michael Gold, John Schinka, Jonathan Hoyne, Aaron Osborne, Steven Sevush, Fiona Crawford

Research output: Contribution to journalArticlepeer-review


The finding of an association between the ε4 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 ε4 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 ε4 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.

Original languageEnglish (US)
Pages (from-to)16-26
Number of pages11
JournalAnnals of the New York Academy of Sciences
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science


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