Apolipoprotein E genotype influences spatial distribution of cerebral microbleeds

Neurobiol Aging. 2014 Apr;35(4):899-905. doi: 10.1016/j.neurobiolaging.2013.09.012. Epub 2013 Oct 9.


In cerebral amyloid angiopathy patients, microbleeds often cluster, mostly occipital, and are associated with apolipoprotein E (APOE) genotype. Microbleeds also frequently occur in the asymptomatic, general population. In this population, we investigated spatial distribution of microbleeds and whether this is influenced by APOE genotype. In 292 persons with microbleeds, we labeled microbleeds on baseline and follow-up magnetic resonance images. We calculated distance between incident and prevalent microbleeds within and between persons and performed lobar segmentation on the magnetic resonance images. Subsequently, we investigated proximity and lobar distribution in strata of APOE genotype. Microbleeds occurred closer within persons than between persons (-42.2 mm, 95% confidence interval, -44.6 to -39.9; p < 0.001). Microbleeds within APOE ε2 and ε4 carriers occurred closer than those in persons with ε3ε3 genotype (-11.9 mm, 95% confidence interval, -24.4 to 0.6; p = 0.06). Persons with ε2 and ε4 alleles had a larger proportion of microbleeds in the occipital lobe than persons with ε3ε3 genotype. Similar to cerebral amyloid angiopathy patients, microbleeds in the general population cluster and the distribution is affected by APOE genotype.

Keywords: APOE; Cerebral microbleeds; Cerebrovascular disease; Epidemiology; Imaging marker; MRI; Population-based; Risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / genetics*
  • Cerebral Amyloid Angiopathy / genetics
  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / pathology
  • Female
  • Genotype*
  • Humans
  • Incidence
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Occipital Lobe
  • Prevalence
  • Risk Factors


  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E