Apolipoprotein E4 allele and Alzheimer disease: examination of allelic association and effect on age at onset in both early- and late-onset cases

Genet Epidemiol. 1995;12(1):83-92. doi: 10.1002/gepi.1370120108.


An increased frequency of the apolipoprotein E type 4 allele (APOE-4) has previously been associated with both late-onset sporadic and late-onset familial Alzheimer disease (AD) [Strittmatter et al. (1993) Proc Natl Acad Sci USA 90:1977-1981; Saunders et al. (1993a) Neurology 43:1467-1472]. To further investigate this association we genotyped affected individuals from 92 separate AD pedigrees including both early- and late-onset cases. An increased frequency of the APOE-4 allele was found only among the late-onset cases, both familial and sporadic, confirming the earlier reports. In addition, age at onset was significantly decreased in the APOE-4 homozygotes (in late onset families) compared to either APOE-4 heterozygotes or individuals not carrying an APOE-4 allele. We also observed a significantly decreased frequency of the APOE-2 allele in both the early- and late-onset familial cases. These results strengthen the argument for a direct role of APOE in susceptibility to AD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Gene Frequency*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lod Score
  • Middle Aged
  • Pedigree


  • Apolipoprotein E4
  • Apolipoproteins E