Sex-dependent effects of the APOE ɛ4 allele on behavioral traits and white matter structures in young adults

Takeuchi, H., Tomita, H., Browne, R., Taki, Y., Kikuchi, Y., Ono, C., Yu, Z., Nouchi, R., Yokoyama, R., Kotozaki, Y., Nakagawa, S., Sekiguchi, A., Iizuka, K., Hanawa, S., Araki, T., Makoto Miyauchi, C., Sakaki, K., Nozawa, T., Ikeda, S., Yokota, S., Magistro, D. ORCID: 0000-0002-2554-3701, Sassa, Y. and Kawashima, R., 2021. Sex-dependent effects of the APOE ɛ4 allele on behavioral traits and white matter structures in young adults. Cerebral Cortex, 31 (1), pp. 672-680. ISSN 1047-3211

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Abstract

The APOE ɛ4 allele is associated with a risk of Alzheimer’s disease in the elderly, with the association being pronounced in females. Conversely, findings of the effects of the APOE ɛ4 allele in young adults are mixed. Here, we investigated the sex–genotype interaction effects of the APOE ɛ4 allele on cognitive functions as well as brain structures among 1258 young adults. After adjusting for multiple comparisons, there were significant effects of the interaction between sex and the number of APOE ɛ4 allele on some speed tasks (e.g., simple processing speed tasks and the reverse Stroop task) as well as on regional white matter volume (rWMV). The observed sex–genotype interaction conferred better cognitive performance and greater rWMV in the anterior frontal and precentral white matter areas in females having more APOE ɛ4 alleles and reduced rWMV in the same areas in male having more APOE ɛ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ɛ4 allele in females.

Item Type: Journal article
Publication Title: Cerebral Cortex
Creators: Takeuchi, H., Tomita, H., Browne, R., Taki, Y., Kikuchi, Y., Ono, C., Yu, Z., Nouchi, R., Yokoyama, R., Kotozaki, Y., Nakagawa, S., Sekiguchi, A., Iizuka, K., Hanawa, S., Araki, T., Makoto Miyauchi, C., Sakaki, K., Nozawa, T., Ikeda, S., Yokota, S., Magistro, D., Sassa, Y. and Kawashima, R.
Publisher: Oxford University Press (OUP)
Date: January 2021
Volume: 31
Number: 1
ISSN: 1047-3211
Identifiers:
NumberType
10.1093/cercor/bhaa251DOI
1368272Other
Rights: © The Author(s) 2020. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Divisions: Schools > School of Science and Technology
Record created by: Laura Ward
Date Added: 05 Jul 2021 14:27
Last Modified: 05 Jul 2021 14:31
URI: http://irep.ntu.ac.uk/id/eprint/43318

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