Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

The Alzheimer's Disease Sequencing Project (ADSP); Alzheimer’s Disease Neuroimaging Initiative (ADNI); The BIOCARD Study Team

doi:10.1002/alz.14343

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

The Alzheimer's Disease Sequencing Project (ADSP), Alzheimer’s Disease Neuroimaging Initiative (ADNI), The BIOCARD Study Team

School of Medicine

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

Abstract

INTRODUCTION: The effects of sex and apolipoprotein E (APOE)—Alzheimer's disease (AD) risk factors—on white matter microstructure are not well characterized. METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)–corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FA_FWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS: Sex differences in FA_FWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Highlights: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water–corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.

Original language	English (US)
Article number	e14343
Journal	Alzheimer's and Dementia
Volume	21
Issue number	1
DOIs	https://doi.org/10.1002/alz.14343
State	Published - Jan 2025

Keywords

Alzheimer's disease
aging
sex differences
white matter disease

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.14343

Cite this

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease. / The Alzheimer's Disease Sequencing Project (ADSP); Alzheimer’s Disease Neuroimaging Initiative (ADNI); The BIOCARD Study Team.
In: Alzheimer's and Dementia, Vol. 21, No. 1, e14343, 01.2025.

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

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title = "Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease",

abstract = "INTRODUCTION: The effects of sex and apolipoprotein E (APOE)—Alzheimer's disease (AD) risk factors—on white matter microstructure are not well characterized. METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)–corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Highlights: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water–corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.",

keywords = "Alzheimer's disease, aging, sex differences, white matter disease",

author = "{The Alzheimer's Disease Sequencing Project (ADSP)} and {Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI)} and {The BIOCARD Study Team} and Amalia Peterson and Aditi Sathe and Dimitrios Zaras and Yisu Yang and Alaina Durant and Deters, {Kacie D.} and Niranjana Shashikumar and Pechman, {Kimberly R.} and Kim, {Michael E.} and Chenyu Gao and {Mohd Khairi}, Nazirah and Zhiyuan Li and Tianyuan Yao and Yuankai Huo and Logan Dumitrescu and Gifford, {Katherine A.} and Wilson, {Jo Ellen} and Cambronero, {Francis E.} and Risacher, {Shannon L.} and Beason-Held, {Lori L.} and Yang An and Konstantinos Arfanakis and Guray Erus and Christos Davatzikos and Duygu Tosun and Toga, {Arthur W.} and Thompson, {Paul M.} and Mormino, {Elizabeth C.} and Mohamad Habes and Di Wang and Panpan Zhang and Kurt Schilling and Marilyn Albert and Walter Kukull and Biber, {Sarah A.} and Landman, {Bennett A.} and Johnson, {Sterling C.} and Julie Schneider and Barnes, {Lisa L.} and Bennett, {David A.} and Jefferson, {Angela L.} and Resnick, {Susan M.} and Saykin, {Andrew J.} and Hohman, {Timothy J.} and Archer, {Derek B.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

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doi = "10.1002/alz.14343",

language = "English (US)",

volume = "21",

journal = "Alzheimer's and Dementia",

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T1 - Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

AU - The Alzheimer's Disease Sequencing Project (ADSP)

AU - Alzheimer’s Disease Neuroimaging Initiative (ADNI)

AU - The BIOCARD Study Team

AU - Peterson, Amalia

AU - Sathe, Aditi

AU - Zaras, Dimitrios

AU - Yang, Yisu

AU - Durant, Alaina

AU - Deters, Kacie D.

AU - Shashikumar, Niranjana

AU - Pechman, Kimberly R.

AU - Kim, Michael E.

AU - Gao, Chenyu

AU - Mohd Khairi, Nazirah

AU - Li, Zhiyuan

AU - Yao, Tianyuan

AU - Huo, Yuankai

AU - Dumitrescu, Logan

AU - Gifford, Katherine A.

AU - Wilson, Jo Ellen

AU - Cambronero, Francis E.

AU - Risacher, Shannon L.

AU - Beason-Held, Lori L.

AU - An, Yang

AU - Arfanakis, Konstantinos

AU - Erus, Guray

AU - Davatzikos, Christos

AU - Tosun, Duygu

AU - Toga, Arthur W.

AU - Thompson, Paul M.

AU - Mormino, Elizabeth C.

AU - Habes, Mohamad

AU - Wang, Di

AU - Zhang, Panpan

AU - Schilling, Kurt

AU - Albert, Marilyn

AU - Kukull, Walter

AU - Biber, Sarah A.

AU - Landman, Bennett A.

AU - Johnson, Sterling C.

AU - Schneider, Julie

AU - Barnes, Lisa L.

AU - Bennett, David A.

AU - Jefferson, Angela L.

AU - Resnick, Susan M.

AU - Saykin, Andrew J.

AU - Hohman, Timothy J.

AU - Archer, Derek B.

PY - 2025/1

Y1 - 2025/1

N2 - INTRODUCTION: The effects of sex and apolipoprotein E (APOE)—Alzheimer's disease (AD) risk factors—on white matter microstructure are not well characterized. METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)–corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Highlights: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water–corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.

AB - INTRODUCTION: The effects of sex and apolipoprotein E (APOE)—Alzheimer's disease (AD) risk factors—on white matter microstructure are not well characterized. METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)–corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Highlights: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water–corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.

KW - Alzheimer's disease

KW - aging

KW - sex differences

KW - white matter disease

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U2 - 10.1002/alz.14343

DO - 10.1002/alz.14343

M3 - Article

C2 - 39711105

AN - SCOPUS:85212794702

SN - 1552-5260

VL - 21

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 1

M1 - e14343

ER -

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

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