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Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele
Author(s) -
Suri Sana,
Mackay Clare E.,
Kelly Michael E.,
Germuska Michael,
Tunbridge Elizabeth M.,
Frisoni Giovanni B.,
Matthews Paul M.,
Ebmeier Klaus P.,
Bulte Daniel P.,
Filippini Nicola
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1755
Subject(s) - apolipoprotein e , hippocampal formation , magnetic resonance imaging , functional magnetic resonance imaging , medicine , cerebral blood flow , psychology , allele , cardiology , neuroscience , disease , biology , genetics , gene , radiology
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 2 ‐inhalation challenge (CO 2 ‐CVR), and the potential contribution of CO 2 ‐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 2 ‐CVR were between ε2‐ and ε4‐carriers, with the latter having the lowest values. Genotype differences in CO 2 ‐CVR accounted for ∼70% of hippocampal BOLD differences between groups. Conclusion Because CO 2 ‐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.