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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.

Original publication




Journal article


Alzheimers Dement

Publication Date





648 - 57.e1


APOE gene, Alzheimer's disease, BOLD, Cerebrovascular reactivity, fMRI, Adult, Apolipoprotein E4, Brain, Brain Mapping, Carbon Dioxide, Cerebrovascular Circulation, Female, Genotype, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Pattern Recognition, Visual, Recognition (Psychology), Young Adult