APOE, TOMM40, and sex interactions on neural network connectivity

Li, Tianqi and Pappas, Colleen and Le, Scott T. and Wang, Qian and Klinedinst, Brandon S. and Larsen, Brittany A. and Pollpeter, Amy and Lee, Ling Yi and Lutz, Mike W. and Gottschalk, William K. and Swerdlow, Russell H. and Nho, Kwangsik and Willette, Auriel A. (2022) APOE, TOMM40, and sex interactions on neural network connectivity. Neurobiology of Aging, 109. pp. 158-165. ISSN 0197-4580, DOI https://doi.org/10.1016/j.neurobiolaging.2021.09.020.

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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.

Item Type: Article
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]
Uncontrolled Keywords: TOMM40; Resting state Fmri; APOE; Default mode network; Aging
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 19 Jul 2022 10:22
Last Modified: 19 Jul 2022 10:22
URI: http://eprints.um.edu.my/id/eprint/33711

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