Longitudinal effects of sex differences and apolipoprotein E genotype on white matter engagement among elderly.

Zhang, H; Zhang, J; Hsu, CL; Hui, ES; Tse, K-H; Mak, HK-F; Shum, DHK

Longitudinal effects of sex differences and apolipoprotein E genotype on white matter engagement among elderly.

Zhang, H Zhang, J Hsu, CL Hui, ES Tse, K-H Mak, HK-F Shum, DHK

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Publisher:: OXFORD UNIV PRESS
Publication Type:: Journal Article
Citation:: Brain Commun, 2025, 7, (4), pp. fcaf278
Issue Date:: 2025

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Field	Value	Language
dc.contributor.author	Zhang, H
dc.contributor.author	Zhang, J
dc.contributor.author	Hsu, CL
dc.contributor.author	Hui, ES
dc.contributor.author	Tse, K-H
dc.contributor.author	Mak, HK-F
dc.contributor.author	Shum, DHK
dc.date.accessioned	2026-01-22T04:22:05Z
dc.date.available	2025-07-16
dc.date.available	2026-01-22T04:22:05Z
dc.date.issued	2025
dc.identifier.citation	Brain Commun, 2025, 7, (4), pp. fcaf278
dc.identifier.issn	2632-1297
dc.identifier.issn	2632-1297
dc.identifier.uri	http://hdl.handle.net/10453/192234
dc.description.abstract	The apolipoprotein E (APOE) ɛ4 allele is the primary genetic risk factor that influences lipid metabolism and contributes to distinctive Alzheimer's disease pathologies, including increased hippocampal atrophy and accelerated cognitive decline. Synaptic dysfunction can occur in APOE4 carriers even before the appearance of any clinical symptoms. Recent evidence has suggested that this genetic risk factor impacts males and females differently. The sex-specific vulnerability for females to cognitive decline, particularly memory, intensifies post-menopause and emphasizes the need for further investigation. White matter abnormalities, APOE4 allele and disruptions in default mode network connectivity serve as early indicators that are crucial for better understanding Alzheimer's disease progression. This study aims to explore relationships between biological sex, APOE4, default mode network-white matter activity and memory function as measured by the Selective Reminding Test. Participants were categorized by risk level on their APOE4 status. Using longitudinal data from the Harvard Aging Brain Study, we examined sex differences in default mode network-white matter engagement among older individuals with and without the APOE4 allele. Our findings demonstrated a significant reduction in default mode network-white matter activity in the right posterior corona radiata in the high-risk group compared to the low-risk group. High-risk females showed reduction in default mode network-white matter activity in the right superior longitudinal fasciculus, which positively correlated with free recall performance, compared to their low-risk counterparts. Unlike females, males showed no significant changes between the low- and high-risk groups. These results underscore the effectiveness of white matter engagement mapping in differentiating longitudinal changes in memory function related to the genetic risk factor APOE4 and biological sex.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	OXFORD UNIV PRESS
dc.relation.ispartof	Brain Commun
dc.relation.isbasedon	10.1093/braincomms/fcaf278
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	3202 Clinical sciences
dc.subject.classification	3209 Neurosciences
dc.subject.classification	5202 Biological psychology
dc.title	Longitudinal effects of sex differences and apolipoprotein E genotype on white matter engagement among elderly.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-01-22T04:22:03Z
pubs.issue	4
pubs.publication-status	Published online
pubs.volume	7
utslib.citation.issue	4

Abstract:

The apolipoprotein E (APOE) ɛ4 allele is the primary genetic risk factor that influences lipid metabolism and contributes to distinctive Alzheimer's disease pathologies, including increased hippocampal atrophy and accelerated cognitive decline. Synaptic dysfunction can occur in APOE4 carriers even before the appearance of any clinical symptoms. Recent evidence has suggested that this genetic risk factor impacts males and females differently. The sex-specific vulnerability for females to cognitive decline, particularly memory, intensifies post-menopause and emphasizes the need for further investigation. White matter abnormalities, APOE4 allele and disruptions in default mode network connectivity serve as early indicators that are crucial for better understanding Alzheimer's disease progression. This study aims to explore relationships between biological sex, APOE4, default mode network-white matter activity and memory function as measured by the Selective Reminding Test. Participants were categorized by risk level on their APOE4 status. Using longitudinal data from the Harvard Aging Brain Study, we examined sex differences in default mode network-white matter engagement among older individuals with and without the APOE4 allele. Our findings demonstrated a significant reduction in default mode network-white matter activity in the right posterior corona radiata in the high-risk group compared to the low-risk group. High-risk females showed reduction in default mode network-white matter activity in the right superior longitudinal fasciculus, which positively correlated with free recall performance, compared to their low-risk counterparts. Unlike females, males showed no significant changes between the low- and high-risk groups. These results underscore the effectiveness of white matter engagement mapping in differentiating longitudinal changes in memory function related to the genetic risk factor APOE4 and biological sex.

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http://hdl.handle.net/10453/192234