Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele

Alzheimers Dement. 2015 Jun;11(6):648-57.e1. doi: 10.1016/j.jalz.2014.05.1755. Epub 2014 Aug 23.


Background: Functional magnetic resonance imaging (MRI) studies have shown that APOE ε2- and ε4-carriers have similar patterns of blood-oxygenation-level-dependent (BOLD) activation suggesting that we need to look beyond the BOLD signal to link APOE's effect on the brain to Alzheimer's disease (AD)-risk.

Methods: We evaluated APOE-related differences in BOLD activation in response to a memory task, cerebrovascular reactivity using a CO2-inhalation challenge (CO2-CVR), and the potential contribution of CO2-CVR to the BOLD signal.

Results: APOE ε4-carriers had the highest task-related hippocampal BOLD signal relative to non-carriers. The largest differences in CO2-CVR were between ε2- and ε4-carriers, with the latter having the lowest values. Genotype differences in CO2-CVR accounted for ∼70% of hippocampal BOLD differences between groups.

Conclusion: Because CO2-CVR gauges vascular health, the differential effect of APOE in young adults may reflect a vascular contribution to the vulnerability of ε4-carriers to late-life pathology. Studies confirming our findings are warranted.

Keywords: APOE gene; Alzheimer's disease; BOLD; Cerebrovascular reactivity; fMRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoprotein E4 / genetics*
  • Brain / physiology*
  • Brain Mapping
  • Carbon Dioxide / metabolism
  • Cerebrovascular Circulation / physiology*
  • Female
  • Genotype
  • Heterozygote*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Oxygen / blood
  • Pattern Recognition, Visual / physiology
  • Recognition, Psychology / physiology
  • Young Adult


  • Apolipoprotein E4
  • Carbon Dioxide
  • Oxygen