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APOE, TOMM40, and sex interactions on neural network connectivity.

Publication ,  Journal Article
Li, T; Pappas, C; Le, ST; Wang, Q; Klinedinst, BS; Larsen, BA; Pollpeter, A; Lee, LY; Lutz, MW; Gottschalk, WK; Swerdlow, RH; Nho, K; Willette, AA
Published in: Neurobiol Aging
January 2022

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.

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Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

January 2022

Volume

109

Start / End Page

158 / 165

Location

United States

Related Subject Headings

  • Sex Characteristics
  • Risk Factors
  • Neurology & Neurosurgery
  • Nerve Net
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Male
  • Humans
  • Heterozygote
  • Haplotypes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, T., Pappas, C., Le, S. T., Wang, Q., Klinedinst, B. S., Larsen, B. A., … Willette, A. A. (2022). APOE, TOMM40, and sex interactions on neural network connectivity. Neurobiol Aging, 109, 158–165. https://doi.org/10.1016/j.neurobiolaging.2021.09.020
Li, Tianqi, Colleen Pappas, Scott T. Le, Qian Wang, Brandon S. Klinedinst, Brittany A. Larsen, Amy Pollpeter, et al. “APOE, TOMM40, and sex interactions on neural network connectivity.Neurobiol Aging 109 (January 2022): 158–65. https://doi.org/10.1016/j.neurobiolaging.2021.09.020.
Li T, Pappas C, Le ST, Wang Q, Klinedinst BS, Larsen BA, et al. APOE, TOMM40, and sex interactions on neural network connectivity. Neurobiol Aging. 2022 Jan;109:158–65.
Li, Tianqi, et al. “APOE, TOMM40, and sex interactions on neural network connectivity.Neurobiol Aging, vol. 109, Jan. 2022, pp. 158–65. Pubmed, doi:10.1016/j.neurobiolaging.2021.09.020.
Li T, Pappas C, Le ST, Wang Q, Klinedinst BS, Larsen BA, Pollpeter A, Lee LY, Lutz MW, Gottschalk WK, Swerdlow RH, Nho K, Willette AA. APOE, TOMM40, and sex interactions on neural network connectivity. Neurobiol Aging. 2022 Jan;109:158–165.
Journal cover image

Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

January 2022

Volume

109

Start / End Page

158 / 165

Location

United States

Related Subject Headings

  • Sex Characteristics
  • Risk Factors
  • Neurology & Neurosurgery
  • Nerve Net
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Male
  • Humans
  • Heterozygote
  • Haplotypes