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© 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.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 CO<inf>2</inf>-inhalation challenge (CO<inf>2</inf>-CVR), and the potential contribution of CO<inf>2</inf>-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 CO<inf>2</inf>-CVR were between ε2- and ε4-carriers, with the latter having the lowest values. Genotype differences in CO<inf>2</inf>-CVR accounted for ∼70% of hippocampal BOLD differences between groups. Conclusion: Because CO<inf>2</inf>-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

DOI

10.1016/j.jalz.2014.05.1755

Type

Journal article

Journal

Alzheimer's and Dementia

Publication Date

01/01/2015

Volume

11

Pages

648 - 657.e1