ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
The effect of Alzheimer's disease genetic factors on limbic white matter microstructure.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Regional juxtacortical microstructural changes and gene expression provide insights into neurodegeneration in Alzheimer's disease.Translational psychiatry · 2026Article
- Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Free water changes and their correlations with multimodal biomarkers in frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Abnormal signal transmission in white matter revealed by resting-state communication connectivity in Alzheimer's disease: A comprehensive cross-sectional and longitudinal study.Translational psychiatry · 2026Article
- Neuroimaging PheWAS and molecular phenotyping implicate PSMC3 in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuroimaging PheWAS and molecular phenotyping implicatemedRxiv : the preprint server for health sciences · 2025Article
- The effect of Alzheimer's disease genetic factors on limbic white matter microstructure.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- White matter microstructure in mid- to late adulthood is influenced by pathway-stratified polygenic risk for Alzheimer's disease.Frontiers in neuroscience · 2025Article
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Authors and funding
48 authors.
Anna LorenzVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Aditi SatheVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Dimitrios ZarasVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Yisu YangVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Alaina DurantVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Michael E KimDepartment of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.
Chenyu GaoDepartment of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Nancy R NewlinDepartment of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.
Karthik RamadassDepartment of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.
Praitayini KanakarajDepartment of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.
Nazirah Mohd KhairiDepartment of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Zhiyuan LiDepartment of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Tianyuan YaoDepartment of Computer Science, Vanderbilt University, Nashville, Tennessee, USA.
Yuankai HuoDepartment of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Logan DumitrescuVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Niranjana ShashikumarVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Kimberly R PechmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Trevor Bryan JacksonVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Abigail W WorkmeisterVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Shannon L RisacherDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Lori L Beason-HeldLaboratory for Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Yang AnLaboratory for Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Konstantinos ArfanakisDepartment of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA.
Guray ErusDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Christos DavatzikosDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Mohamad HabesGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Di WangUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
Arthur W TogaLaboratory of Neuroimaging, USC Stevens Institute of Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
Elizabeth C MorminoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Panpan ZhangVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Kurt SchillingDepartment of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Alzheimer's Disease Neuroimaging Initiative (ADNI)The BIOCARD Study TeamThe Alzheimer's Disease Sequencing Project (ADSP)
Marilyn AlbertDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Walter KukullNational Alzheimer's Coordinating Center, University of Washington, Seattle, Washington, USA.
Sarah A BiberNational Alzheimer's Coordinating Center, University of Washington, Seattle, Washington, USA.
Bennett A LandmanDepartment of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Sterling C JohnsonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Barbara BendlinWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Julie SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Lisa L BarnesRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Angela L JeffersonVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Susan M ResnickIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Andrew J SaykinDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Derek B ArcherVanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Funding
Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7MAlzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2MVIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1MProject 2 MeasurementU19AG033655 · NIA · JOHNS HOPKINS UNIVERSITY · PI JUAN TRONCOSO · 2014 to 2026
$51.5MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MNational Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MTREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SWEET, ROBERT A · 1985 to 2019
$43.0MTHE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1MAlzheimer's Association IIRG-08-88733Alzheimer's Drug Discovery FoundationAlzheimer's Therapeutic Research Institute at the University of Southern CaliforniaAraclon BiotechBioClinica, Inc.BiogenBristol-Myers Squibb CompanyCereSpir, Inc.CIHRCogstateDOD ADNI W81XWH-12-2-0012Elan Pharmaceuticals, Inc.Eli Lilly and CompanyFujirebioGE HealthcareGenentech, Inc.Illinois Department of Public HealthIXICO Ltd.Janssen Alzheimer Immunotherapy Research & Development, LLC.Johnson & Johnson Pharmaceutical Research & Development LLC.Laboratory for Neuro Imaging at the University of Southern CaliforniaLumosityLundbeckMeso Scale Diagnostics, LLC.NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR002243NeuroRx ResearchNeurotrack TechnologiesNIA NIH HHS AG021155NIA NIH HHS AG0271761NIA NIH HHS AG037639NIA NIH HHS AG054047NIA NIH HHS K01 AG073584NIA NIH HHS P20 AG068024NIA NIH HHS P20 AG068053NIA NIH HHS P20 AG068077NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG049638NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072946NIA NIH HHS P30-AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072975NIA NIH HHS P30AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30AG10161NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS P50 AG047266NIA NIH HHS P50 AG047270NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01AG017917NIA NIH HHS R01 AG021155NIA NIH HHS R01 AG034962NIA NIH HHS R01-AG034962NIA NIH HHS R01 AG037639NIA NIH HHS R01 AG054047NIA NIH HHS R01 AG056405NIA NIH HHS R01AG056405NIA NIH HHS R01 AG056534NIA NIH HHS R01-AG056534NIA NIH HHS R01 AG059716NIA NIH HHS R01 AG064233NIA NIH HHS R01AG064233NIA NIH HHS R01 AG067482NIA NIH HHS R01AG067482NIA NIH HHS R01 AG068193NIA NIH HHS R01 AG073439NIA NIH HHS R01 AG080821NIA NIH HHS R01 AG085571NIA NIH HHS R01AG15819NIA NIH HHS R56 AG037639NIA NIH HHS RF1 AG054047NIA NIH HHS U01 AG024904NIA NIH HHS U19 AG033655NIA NIH HHS U19-AG03655NIA NIH HHS U24 AG072122NIA NIH HHS U24 AG074855NIA NIH HHS UH2NS100599NIA NIH HHS UH3NS100599NIBIB NIH HHS K01 EB032898NIBIB NIH HHS R01 EB017230NIH HHS S10 OD023680NIH HHS U01 AG024904NINDS NIH HHS U01 NS100599NINDS NIH HHS UH2 NS100599NINDS NIH HHS UH3 NS100599Northern California Institute for Research and EducationNovartis Pharmaceuticals CorporationPfizer Inc.Piramal ImagingServierTakeda Pharmaceutical CompanyTransition TherapeuticsVanderbilt Clinical Translational Science Award S10-OD023680Vanderbilt Memory and Aging ProjectVanderbilt's High-Performance Computer Cluster for Biomedical ResearchVanderbilt University Medical Center
Abstract
introductionWhite matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.
methodsTo evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores (PGSs) and WM metrics, and interactions with cognitive status.
resultsAD PGSs, variants in TMEM106B, PTK2B, WNT3, and apolipoprotein E (APOE), and interactions involving MS4A6A were significantly linked to WM microstructure. DISCUSSION: These findings implicate AD-related genetic factors related to neurodevelopment (WNT3), lipid metabolism (APOE), and inflammation (TMEM106B, PTK2B, MS4A6A) that contribute to alternations in WM microstructure in older adults. HIGHLIGHTS: AD risk variants in TMEM106B, PTK2B, WNT3, and APOE genes showed distinct associations with limbic FW-corrected WM microstructure metrics. Interaction effects were observed between MS4A6A variants and cognitive status. PGS for AD was associated with higher FW content in the limbic system.
Indexed as
Alzheimer DiseaseLimbic SystemWhite MatterAgedAged, 80 and overApolipoproteins ECohort StudiesDiffusion Tensor ImagingFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedRisk FactorsApolipoproteins EAlzheimer's diseasediffusion MRIfree watergenetic risk variantspolygenic riskwhite matter microstructure
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