APOE, TOMM40, and sex interactions on neural network connectivity.
Aging
/ genetics
Alzheimer Disease
/ genetics
Apolipoproteins E
/ genetics
Cognition
Epistasis, Genetic
/ genetics
Female
Genotype
Haplotypes
Heterozygote
Humans
Male
Middle Aged
Mitochondrial Precursor Protein Import Complex Proteins
/ genetics
Nerve Net
/ physiology
Risk Factors
Sex Characteristics
APOE
Aging
Default mode network
Resting state Fmri
TOMM40
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
03
02
2021
revised:
21
09
2021
accepted:
22
09
2021
pubmed:
6
11
2021
medline:
19
2
2022
entrez:
5
11
2021
Statut:
ppublish
Résumé
The Apolipoprotein E ε4 (APOE ε4) 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 ε4 was associated with less strength in multiple networks, while '650 G versus A carriage was related to more language comprehension network strength. In APOE ε4 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 ε4 carriers depending on sex.
Identifiants
pubmed: 34740077
pii: S0197-4580(21)00301-8
doi: 10.1016/j.neurobiolaging.2021.09.020
pmc: PMC8694046
mid: NIHMS1754780
pii:
doi:
Substances chimiques
Apolipoproteins E
0
Mitochondrial Precursor Protein Import Complex Proteins
0
TOMM40 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-165Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R00 AG047282
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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