Sex-Dependent Effects of the APOE ϵ4 Allele on Behavioral Traits and White Matter Structures in Young Adults

Hikaru Takeuchi; Hiroaki Tomita; Ryan Browne; Yasuyuki Taki; Yoshie Kikuchi; Chiaki Ono; Zhiqian Yu; Rui Nouchi; Ryoichi Yokoyama; Yuka Kotozaki; Seishu Nakagawa; Atsushi Sekiguchi; Kunio Iizuka; Sugiko Hanawa; Tsuyoshi Araki; Carlos Makoto Miyauchi; Kohei Sakaki; Takayuki Nozawa; Shigeyuki Ikeda; Susumu Yokota; Daniele Magistro; Yuko Sassa; Ryuta Kawashima

doi:10.1093/cercor/bhaa251

Sex-Dependent Effects of the APOE ϵ4 Allele on Behavioral Traits and White Matter Structures in Young Adults

Hikaru Takeuchi, Hiroaki Tomita, Ryan Browne, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Rui Nouchi, Ryoichi Yokoyama, Yuka Kotozaki, Seishu Nakagawa, Atsushi Sekiguchi, Kunio Iizuka, Sugiko Hanawa, Tsuyoshi Araki, Carlos Makoto Miyauchi, Kohei Sakaki, Takayuki Nozawa, Shigeyuki Ikeda, Susumu YokotaDaniele Magistro, Yuko Sassa, Ryuta Kawashima

Division for Experimental Natural Science

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

The APOE ϵ4 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 ϵ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ϵ4 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 ϵ4 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 ϵ4 alleles and reduced rWMV in the same areas in male having more APOE ϵ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ϵ4 allele in females.

Original language	English
Pages (from-to)	672-680
Number of pages	9
Journal	Cerebral Cortex
Volume	31
Issue number	1
DOIs	https://doi.org/10.1093/cercor/bhaa251
Publication status	Published - Jan 1 2021

All Science Journal Classification (ASJC) codes

Cognitive Neuroscience
Cellular and Molecular Neuroscience

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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., Miyauchi, C. M., Sakaki, K., Nozawa, T., Ikeda, S., ... Kawashima, R. (2021). Sex-Dependent Effects of the APOE ϵ4 Allele on Behavioral Traits and White Matter Structures in Young Adults. Cerebral Cortex, 31(1), 672-680. https://doi.org/10.1093/cercor/bhaa251

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, Miyauchi, CM, Sakaki, K, Nozawa, T, Ikeda, S, Yokota, S, Magistro, D, Sassa, Y & Kawashima, R 2021, 'Sex-Dependent Effects of the APOE ϵ4 Allele on Behavioral Traits and White Matter Structures in Young Adults', Cerebral Cortex, vol. 31, no. 1, pp. 672-680. https://doi.org/10.1093/cercor/bhaa251

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title = "Sex-Dependent Effects of the APOE ϵ4 Allele on Behavioral Traits and White Matter Structures in Young Adults",

abstract = "The APOE ϵ4 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 ϵ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ϵ4 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 ϵ4 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 ϵ4 alleles and reduced rWMV in the same areas in male having more APOE ϵ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ϵ4 allele in females.",

author = "Hikaru Takeuchi and Hiroaki Tomita and Ryan Browne and Yasuyuki Taki and Yoshie Kikuchi and Chiaki Ono and Zhiqian Yu and Rui Nouchi and Ryoichi Yokoyama and Yuka Kotozaki and Seishu Nakagawa and Atsushi Sekiguchi and Kunio Iizuka and Sugiko Hanawa and Tsuyoshi Araki and Miyauchi, {Carlos Makoto} and Kohei Sakaki and Takayuki Nozawa and Shigeyuki Ikeda and Susumu Yokota and Daniele Magistro and Yuko Sassa and Ryuta Kawashima",

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AU - Taki, Yasuyuki

AU - Kikuchi, Yoshie

AU - Ono, Chiaki

AU - Yu, Zhiqian

AU - Nouchi, Rui

AU - Yokoyama, Ryoichi

AU - Kotozaki, Yuka

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AU - Sekiguchi, Atsushi

AU - Iizuka, Kunio

AU - Hanawa, Sugiko

AU - Araki, Tsuyoshi

AU - Miyauchi, Carlos Makoto

AU - Sakaki, Kohei

AU - Nozawa, Takayuki

AU - Ikeda, Shigeyuki

AU - Yokota, Susumu

AU - Magistro, Daniele

AU - Sassa, Yuko

AU - Kawashima, Ryuta

PY - 2021/1/1

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N2 - The APOE ϵ4 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 ϵ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ϵ4 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 ϵ4 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 ϵ4 alleles and reduced rWMV in the same areas in male having more APOE ϵ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ϵ4 allele in females.

AB - The APOE ϵ4 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 ϵ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ϵ4 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 ϵ4 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 ϵ4 alleles and reduced rWMV in the same areas in male having more APOE ϵ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ϵ4 allele in females.

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Sex-Dependent Effects of the APOE ϵ4 Allele on Behavioral Traits and White Matter Structures in Young Adults

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