Opposite Neural Trajectories of Apolipoprotein E ϵ4 and ϵ2 Alleles with Aging Associated with Different Risks of Alzheimer's Disease. Cereb Cortex 2016 Apr;26(4):1421-1429
Date
10/23/2014Pubmed ID
25336599Pubmed Central ID
PMC4785940DOI
10.1093/cercor/bhu237Scopus ID
2-s2.0-84963928909 (requires institutional sign-in at Scopus site) 62 CitationsAbstract
The apolipoprotein E (APOE) ϵ4 allele is a confirmed genetic risk factor and the APOE ϵ2 allele is a protective factor related to late-onset Alzheimer's disease (AD). Intriguingly, recent studies demonstrated similar brain function alterations between APOE ϵ2 and ϵ4 alleles, despite their opposite susceptibilities to AD. To address this apparent discrepancy, we recruited 129 cognitively normal elderly subjects, including 36 ϵ2 carriers, 44 ϵ3 homozygotes, and 49 ϵ4 carriers. All subjects underwent resting-state functional MRI scans. We hypothesized that aging could influence the APOE ϵ2 and ϵ4 allele effects that contribute to their appropriate AD risks differently. Using the stepwise regression analysis, we demonstrated that although both ϵ2 and ϵ4 carriers showed decreased functional connectivity (FC) compared with ϵ3 homozygotes, they have opposite aging trajectories in the default mode network-primarily in the bilateral anterior cingulate cortex. As age increased, ϵ2 carriers showed elevated FC, whereas ϵ4 carriers exhibited decreased FC. Behaviorally, the altered DMN FC positively correlated with information processing speed in both ϵ2 and ϵ4 carriers. It is suggested that the opposite aging trajectories between APOE ϵ2 and ϵ4 alleles in the DMN may reflect the antagonistic pleiotropic properties and associate with their different AD risks.
Author List
Shu H, Shi Y, Chen G, Wang Z, Liu D, Yue C, Ward BD, Li W, Xu Z, Chen G, Guo Q, Xu J, Li SJ, Zhang ZMESH terms used to index this publication - Major topics in bold
AgedAging
Alzheimer Disease
Apolipoprotein E2
Apolipoprotein E4
Brain
Brain Mapping
Female
Genetic Predisposition to Disease
Gyrus Cinguli
Humans
Magnetic Resonance Imaging
Male
Neural Pathways
Neuropsychological Tests
