The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals

Neurobiol Aging. 2020 Nov:95:104-114. doi: 10.1016/j.neurobiolaging.2020.06.015. Epub 2020 Jun 29.


Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability.

Trial registration: NCT01835717 NCT02198586.

Keywords: APOE; Alzheimer’s disease (AD); Cerebral microbleeds (CMBs); Magnetic resonance imaging (MRI); White matter hyperintensities (WMH).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Apolipoproteins E / genetics*
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / psychology
  • Cognition*
  • Female
  • Genetic Association Studies*
  • Genotype*
  • Homozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • White Matter / diagnostic imaging
  • White Matter / pathology


  • Apolipoproteins E

Associated data