Sex-Dependent Effects of the<i>APOE</i>ɛ4 Allele on Behavioral Traits and White Matter Structures in Young Adults

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

doi:10.1093/cercor/bhaa251

Cited by 6 publications

(2 citation statements)

References 44 publications

(23 reference statements)

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“…The lack of concordance between astroglial-plaque interactions and measures of AD-related pathology suggest the possibility of inherent sex and APOE genotype effects. Indeed, there are numerous observations of sex × APOE interactions across multiple domains in the absence of significant Ab pathology in rodents and humans [32][33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice

Stephen

Breningstall

Suresh

et al. 2022

J Neuroinflammation

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The most significant genetic risk factor for developing late-onset Alzheimer’s disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here, we show astroglial interactions with amyloid plaques in the EFAD transgenic mouse model of AD. Using confocal microscopy, we observed significantly lower levels of astrocytic plaque coverage and plaque compaction (beneficial effects of glial barrier formation) with APOE4 genotype and female sex. Conversely, neurite damage and astrocyte activation in the plaque environment were significantly higher in APOE4 carriers and female mice. Astrocyte coverage of plaques was highest in APOE3 males and poorest in APOE4 females. Collectively, our findings provide new insights into the roles of astroglia and highlight the importance of addressing independent and interactive effects of APOE genotype and biological sex in understanding processes contributing to AD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice

Stephen

Breningstall

Suresh

et al. 2022

J Neuroinflammation

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“…The scans were checked for noticeable brain lesions and tumors in this experiment, but no subjects had such apparent lesions or tumors. These descriptions are mostly obtained from our previously published work [76]. The participant's socio-demographic characteristics are presented in Table 1.…”

Section: Participantsmentioning

confidence: 99%

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Lead exposure is associated with functional and microstructural changes in the healthy human brain

et al. 2021

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Lead is a toxin known to harm many organs in the body, particularly the central nervous system, across an individual’s lifespan. To date, no study has yet investigated the associations between body lead level and the microstructural properties of gray matter areas, and brain activity during attention-demanding tasks. Here, utilizing data of diffusion tensor imaging, functional magnetic resonance imaging and cognitive measures among 920 typically developing young adults, we show greater hair lead levels are weakly but significantly associated with (a) increased working memory-related activity in the right premotor and pre-supplemental motor areas, (b) lower fractional anisotropy (FA) in white matter areas near the internal capsule, (c) lower mean diffusivity (MD) in the dopaminergic system in the left hemisphere and other widespread contingent areas, and (d) greater MD in the white matter area adjacent to the right fusiform gyrus. Higher lead levels were also weakly but significantly associated with lower performance in tests of high-order cognitive functions, such as the psychometric intelligence test, greater impulsivity measures, and higher novelty seeking and extraversion. These findings reflect the weak effect of daily lead level on the excitability and microstructural properties of the brain, particularly in the dopaminergic system.

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Sex-Dependent Effects of theAPOEɛ4 Allele on Behavioral Traits and White Matter Structures in Young Adults

Cited by 6 publications

References 44 publications

APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice

APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice

Untitled

Lead exposure is associated with functional and microstructural changes in the healthy human brain

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