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Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele

Suri, San, Mackay, Clare E., Kelly, Michael E., Germuska, Michael, Tunbridge, Elizabeth M., Frisoni, Giovanni B., Matthews, Paul M., Ebmeier, Klaus P., Bulte, Daniel P. and Filippini, Nicola 2015. Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele. Alzheimer's and Dementia 11 (6) , pp. 648-657. 10.1016/j.jalz.2014.05.1755

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: APOE gene; Alzheimer's disease; BOLD; Cerebrovascular reactivity; fMRI
Publisher: The Alzheimer's Association
ISSN: 1552-5260
Last Modified: 05 Mar 2019 14:00

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