APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults

Alzheimers Dement. 2019 Feb;15(2):258-266. doi: 10.1016/j.jalz.2018.08.007. Epub 2018 Oct 12.


Introduction: Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology.

Methods: We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9-108.2 years at death) with and without dementia. Excluding ε2/ε4 carriers, multivariable regressions for each CVD-related neuropathology compared ε4 and ε2 carriers to ε3/ε3 carriers adjusting for confounders including age and Alzheimer's neuropathology.

Results: Three hundred forty-two individuals (24.7%; ∼87.7 years at death; 39.9% nondemented) were ε3/ε4 or ε4/ε4, and 180 (13.0%; ∼89.9 years at death; 66.6% nondemented) were ε2/ε3 or ε2/ε2. ε4 carriers had higher odds of macroinfarcts (odds ratio = 1.41, 95% confidence interval: 1.02-1.94, P = .03), whereas ε2 carriers had higher odds of moderate-to-severe arteriolosclerosis (odds ratio = 1.68, 95% confidence interval: 1.15-2.45, P = .006) compared to ε3/ε3 carriers. Age-stratified analyses suggested that these relationships were driven by ε4 carriers <90 years at death and ε2 carriers ≥90 years at death, respectively.

Discussion: APOE differentially affects type and timing of CVD-related neuropathology.

Keywords: APOE ε2 allele; APOE ε4 allele; Cerebrovascular disease; Neuropathology; Oldest old.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics*
  • Cerebrovascular Disorders / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype*
  • Heterozygote
  • Humans
  • Male
  • Risk Factors


  • Apolipoproteins E