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

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

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

Alzheimers Dement. 2024 Dec 22. doi: 10.1002/alz.14343. Online ahead of print.

Authors

Amalia Peterson^{1

2}, Aditi Sathe¹, Dimitrios Zaras¹, Yisu Yang¹, Alaina Durant¹, Kacie D Deters³, Niranjana Shashikumar¹, Kimberly R Pechman¹, Michael E Kim⁴, Chenyu Gao⁵, Nazirah Mohd Khairi⁵, Zhiyuan Li⁵, Tianyuan Yao⁴, Yuankai Huo^{4

5}, Logan Dumitrescu^{1

2

6

7}, Katherine A Gifford^{1

2}, Jo Ellen Wilson^{1

8

9}, Francis E Cambronero¹, Shannon L Risacher^{10

11}, Lori L Beason-Held¹², Yang An¹², Konstantinos Arfanakis^{13

14

15}, Guray Erus¹⁶, Christos Davatzikos¹⁶, Duygu Tosun¹⁷, Arthur W Toga¹⁸, Paul M Thompson¹⁹, Elizabeth C Mormino²⁰, Mohamad Habes²¹, Di Wang²¹, Panpan Zhang^{1

22}, Kurt Schilling^{23

24}; Alzheimer's Disease Neuroimaging Initiative (ADNI); BIOCARD Study Team; Alzheimer's Disease Sequencing Project (ADSP); Marilyn Albert²⁵, Walter Kukull²⁶, Sarah A Biber²⁶, Bennett A Landman^{2

4

5

7

23

24

27}, Sterling C Johnson^{28

29}, Julie Schneider¹⁴, Lisa L Barnes¹⁴, David A Bennett¹⁴, Angela L Jefferson^{1

2

4}, Susan M Resnick¹², Andrew J Saykin^{10

11}, Timothy J Hohman^{1

2

6

7}, Derek B Archer^{1

2

6

7}

Affiliations

¹ Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
² Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Department of Integrative Biology and Physiology, University of California, Los Angeles, California, USA.
⁴ Department of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.
⁵ Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee, USA.
⁶ Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷ Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁸ Department of Psychiatry and Behavioral Sciences, Center for Cognitive Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁹ Veteran's Affairs, Geriatric Research, Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
¹⁰ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹¹ Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹² Laboratory for Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
¹³ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA.
¹⁴ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
¹⁵ Department of Diagnostic Radiology, Rush University Medical Center, Chicago, Illinois, USA.
¹⁶ Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁷ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
¹⁸ Laboratory of Neuroimaging, USC Stevens Institute of Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁹ Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
²⁰ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
²¹ Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
²² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²³ Department of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁴ Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁵ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
²⁶ National Alzheimer's Coordinating Center, University of Washington, Seattle, Washington, USA.
²⁷ Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
²⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
²⁹ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

PMID: 39711105
DOI: 10.1002/alz.14343

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.

Keywords: Alzheimer's disease; aging; sex differences; white matter disease.

Abstract

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