APOE, TOMM40, and sex interactions on neural network connectivity
Document Type
Article
Publication Date
1-1-2022
Abstract
The Apolipoprotein E epsilon 4 (APOE epsilon 4) haplotype is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The Translocase of Outer Mitochondrial Membrane-40 (TOMM40) gene maintains cellular bioenergetics, which is disrupted in AD. TOMM40 rs2075650 ('650) G versus A carriage is consistently related to neural and cognitive outcomes, but it is unclear if and how it interacts with APOE. We examined 21 orthogonal neural networks among 8,222 middle-aged to aged participants in the UK Biobank cohort. ANOVA and multiple linear regression tested main effects and interactions with APOE and TOMM40 `650 genotypes, and if age and sex acted as moderators. APOE epsilon 4 was associated with less strength in multiple networks, while `650 G versus A carriage was related to more language comprehension network strength. In APOE epsilon 4 carriers, `650 G-carriage led to less network strength with increasing age, while in non-G-carriers this was only seen in women but not men. TOMM40 may shift what happens to network activity in aging APOE epsilon 4 carriers depending on sex. (C) 2021 Elsevier Inc. All rights reserved.
Keywords
TOMM40, Resting state Fmri, APOE, Default mode network, Aging
Divisions
fac_med
Funders
Iowa State University,United States Department of Health & Human Services National Institutes of Health (NIH) - USA [Grant No: R00 AG047282],Alzheimer's Association Research Grant to Promote Diversity (AARG-D) [Grant No: 17-529552]
Publication Title
Neurobiology of Aging
Volume
109
Publisher
Elsevier Science Inc
Publisher Location
STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA