Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease.
Overview
and 28 other authors
Konstantinos Arfanakis10,11,12, Guray Erus13, Christos Davatzikos13, Mohamad Habes14, Di Wang14, Duygu Tosun15, Arthur W. Toga16, Paul M. Thompson17, Elizabeth C. Mormino18, Panpan Zhang1,19, Kurt Schilling20,21, Marilyn Albert22, Walter Kukull23, Sarah A. Biber23, Bennett A. Landman2,20,21,24, Sterling C. Johnson25,26, Barbara Bendlin25,26, Julie Schneider11, David A. Bennett11, Angela L. Jefferson1,5,6, Susan M. Resnick9, Andrew J. Saykin7,8, Jennifer E. Below1,2,27, Timothy J. Hohman1,2,5,6, Derek B. Archer1,2,5,6, Alzheimer's Disease Neuroimaging Initiative (ADNI), The BIOCARD Study Team (BIOCARD), The Alzheimer's Disease Sequencing Project (ADSP)27 affiliations
- Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine Nashville Tennessee USA
- Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville Tennessee USA
- Department of Computer Science Vanderbilt University Nashville Tennessee USA
- Department of Electrical and Computer Engineering Vanderbilt University Nashville Tennessee USA
- Department of Neurology Vanderbilt University Medical Center Nashville Tennessee USA
- Vanderbilt Brain Institute Vanderbilt University Medical Center Nashville Tennessee USA
- Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA
- Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana USA
- Laboratory for Behavioral Neuroscience National Institute on Aging National Institutes of Health Baltimore Maryland USA
- Department of Biomedical Engineering Illinois Institute of Technology Chicago Illinois USA
- Rush Alzheimer's Disease Center Rush University Medical Center Chicago Illinois USA
- Department of Diagnostic Radiology Rush University Medical Center Chicago Illinois USA
- Department of Radiology University of Pennsylvania Philadelphia Pennsylvania USA
- Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health Science Center San Antonio Texas USA
- Department of Radiology and Biomedical Imaging University of California San Francisco California USA
- Laboratory of Neuroimaging USC Stevens Institute of Neuroimaging and Informatics Keck School of Medicine University of Southern California Los Angeles California USA
- 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
- Department of Neurology and Neurological Sciences Stanford University School of Medicine Stanford California USA
- Department of Biostatistics Vanderbilt University Medical Center Nashville Tennessee USA
- Department of Radiology & Radiological Sciences Vanderbilt University Medical Center Nashville Tennessee USA
- Vanderbilt University Medical Center Vanderbilt University Institute of Imaging Science Nashville Tennessee USA
- Department of Neurology Johns Hopkins School of Medicine Baltimore Maryland USA
- National Alzheimer's Coordinating Center University of Washington Seattle Washington USA
- Department of Biomedical Engineering Vanderbilt University Nashville Tennessee USA
- Wisconsin Alzheimer's Disease Research Center School of Medicine and Public Health University of Wisconsin Madison Wisconsin USA
- Wisconsin Alzheimer's Institute School of Medicine and Public Health University of Wisconsin Madison Wisconsin USA
- Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA
Abstract
INTRODUCTION: Limbic white matter (WM) abnormalities are prevalent in aging and Alzheimer's disease (AD), but genetic drivers are unclear.
METHODS: In 2614 older adults (mean age ± SD: 73.7 ± 9.8 years; 26% cognitively impaired) from seven harmonized cohorts enriched for cognitive impairment, we quantified free‐water–corrected diffusion MRI (dMRI) metrics in seven limbic tracts. We estimated single nucleotide polymorphism (SNP) heritability, performed cohort genome‐wide association studies (GWASs) with meta‐analysis, evaluated shared genetic architecture and enriched pathways, and assessed AD relevance using brain RNA‐seq data.
RESULTS: Limbic WM is heritable (h2 = 0.26–0.60; pFDR < 0.05). Meta‐GWAS identified six loci (p < 5 × 10− 8), including a signal implicating CDH19, an oligodendrocyte‐enriched
DISCUSSION: Limbic WM microstructure is genetically influenced and links oligodendrocyte and vascular‐inflammatory biology to AD‐relevant outcomes.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Zenodo 13863955
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Recorded: type, language, journal, volume, issue, pages, dates, 48 authors, 6 keywords, 12 MeSH terms, 3 funders, 73 references.
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This paper
Lorenz, A. S., Sathe, A., Yang, Y., Durant, A., Wu, Y., Kim, M. E., Gao, C., Newlin, N. R., Ramadass, K., Kanakaraj, P., Khairi, N. M., Li, Z., Yao, T., Huo, Y., Dumitrescu, L., Shashikumar, N., Pechman, K. R., Risacher, S. L., Beason‐Held, L. L., . . . The Alzheimer's Disease Sequencing Project (ADSP). (2026). Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease. Alzheimer's & dementia : the journal of the Alzheimer's Association, 22(7), e71630. https://
BibTeX
@article{lorenz2026genet
author = {Lorenz, Anna S and Sathe, Aditi and Yang, Yisu and Durant, Alaina and Wu, Yiyang and Kim, Michael E. and Gao, Chenyu and Newlin, Nancy R. and Ramadass, Karthik and Kanakaraj, Praitayini and Khairi, Nazirah Mohd and Li, Zhiyuan and Yao, Tianyuan and Huo, Yuankai and Dumitrescu, Logan and Shashikumar, Niranjana and Pechman, Kimberly R. and Risacher, Shannon L. and Beason‐Held, Lori L. and An, Yang and Arfanakis, Konstantinos and Erus, Guray and Davatzikos, Christos and Habes, Mohamad and Wang, Di and Tosun, Duygu and Toga, Arthur W. and Thompson, Paul M. and Mormino, Elizabeth C. and Zhang, Panpan and Schilling, Kurt and Albert, Marilyn and Kukull, Walter and Biber, Sarah A. and Landman, Bennett A. and Johnson, Sterling C. and Bendlin, Barbara and Schneider, Julie and Bennett, David A. and Jefferson, Angela L. and Resnick, Susan M. and Saykin, Andrew J. and Below, Jennifer E. and Hohman, Timothy J. and Archer, Derek B. and {Alzheimer's Disease Neuroimaging Initiative (ADNI)} and {The BIOCARD Study Team (BIOCARD)} and {The Alzheimer's Disease Sequencing Project (ADSP)}},
title = {{Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
month = jul,
volume = {22},
number = {7},
pages = {e71630},
publisher = {Wiley},
issn = {1552-5260},
doi = {10.1002/
url = {https://
pmid = {42410730},
pmcid = {PMC13338108}
}
RIS
TY - JOUR
AU - Lorenz, Anna S
AU - Sathe, Aditi
AU - Yang, Yisu
AU - Durant, Alaina
AU - Wu, Yiyang
AU - Kim, Michael E.
AU - Gao, Chenyu
AU - Newlin, Nancy R.
AU - Ramadass, Karthik
AU - Kanakaraj, Praitayini
AU - Khairi, Nazirah Mohd
AU - Li, Zhiyuan
AU - Yao, Tianyuan
AU - Huo, Yuankai
AU - Dumitrescu, Logan
AU - Shashikumar, Niranjana
AU - Pechman, Kimberly R.
AU - Risacher, Shannon L.
AU - Beason‐Held, Lori L.
AU - An, Yang
AU - Arfanakis, Konstantinos
AU - Erus, Guray
AU - Davatzikos, Christos
AU - Habes, Mohamad
AU - Wang, Di
AU - Tosun, Duygu
AU - Toga, Arthur W.
AU - Thompson, Paul M.
AU - Mormino, Elizabeth C.
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 - Bendlin, Barbara
AU - Schneider, Julie
AU - Bennett, David A.
AU - Jefferson, Angela L.
AU - Resnick, Susan M.
AU - Saykin, Andrew J.
AU - Below, Jennifer E.
AU - Hohman, Timothy J.
AU - Archer, Derek B.
AU - Alzheimer's Disease Neuroimaging Initiative (ADNI)
AU - The BIOCARD Study Team (BIOCARD)
AU - The Alzheimer's Disease Sequencing Project (ADSP)
TI - Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease
T2 - Alzheimer's & dementia : the journal of the Alzheimer's Association
J2 - Alzheimers Dement
PY - 2026
DA - 2026/
VL - 22
IS - 7
SP - e71630
SN - 1552-5260
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
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