Apolipoprotein E ∈4 association with dementia in a population-based study: The Framingham Study

Academic Article


  • Apolipoprotein E type 4 allele (apoE ∈4) is associated with Alzheimer's disease (AD) in the late-onset familial form and in sporadic cases, but the age-associated risk in a randomly sampled elderly population is not established. We examined the association of apoE ∈4 with AD and other dementias (mainly multi-infarct or dementia following stroke) in 1,030 persons aged 71 to 100 years in the population-based Framingham Study cohort. Kaplan-Meier survival analysis revealed that 55% of the apoE ∈4/∈4 homozygotes developed AD by age 80, whereas 21% of apoE ∈3/∈4 heterozygotes developed AD by age 85, and 9% of those without a 4 allele developed AD by age 85 years. In comparison with persons without a 4 allele, the risk ratio for AD was 3.7 (95% CI = 1.9 to 7.5) for apoE ∈3/∈4 heterozygotes and 30.1 (95% CI - 10.7 to 84.4) for apoE ∈4 homozygotes. ApoE ∈2 (2/2, 2/3, or 2/4 genotypes) was associated with an absence of AD. One-half (n = 21) of the 43 AD patients were either homozygous or heterozygous for apoE ∈4. We found evidence for an association of apoE ∈4 with other dementia, primarily multi-infarct dementia and stroke. The risk ratio is 2.3 (95% CI = 0.9 to 6.1) for non-AD dementias among persons with apoE ∈3/∈4. Although the apoE ∈4 allele is a potent risk factor for AD and may be associated with other forms of dementia, most apoE ∈4 carriers do not develop dementia, and about one-half of AD is not apoE ∈4 associated. The low positive predictive value of this marker (0.10) suggests that use of apoE genotyping as a screening test for AD is not supported.
  • Published In

  • Neurology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Myers RH; Schaefer EJ; Wilson PWF; D'Agostino R; Ordovas JM; Espino A; Au R; White RF; Knoefel JE; Cobb JL
  • Start Page

  • 673
  • End Page

  • 677
  • Volume

  • 46
  • Issue

  • 3