APOE, TOMM40, and sex interactions on neural network connectivity

• Main Authors: Li, Tianqi, Pappas, Colleen, Le, Scott T., Wang, Qian, Klinedinst, Brandon S., Larsen, Brittany A., Pollpeter, Amy, Lee, Ling Yi, Lutz, Mike W., Gottschalk, William K., Swerdlow, Russell H., Nho, Kwangsik, Willette, Auriel A.
• Format: Article
• Published: Elsevier Science Inc 2022
• Subjects: R Medicine (General); RC Internal medicine
• Online Access: http://eprints.um.edu.my/33711/
• Institution: Universiti Malaya

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.