OSCR

Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease.

Overview

Authors: Anna S Lorenz1,2, Aditi Sathe1, Yisu Yang1, Alaina Durant1, Yiyang Wu1, Michael E. Kim3, Chenyu Gao4, Nancy R. Newlin3, Karthik Ramadass3,4, Praitayini Kanakaraj3, Nazirah Mohd Khairi4, Zhiyuan Li4, Tianyuan Yao3, Yuankai Huo4, Logan Dumitrescu1,2,5,6, Niranjana Shashikumar1, Kimberly R. Pechman1, Shannon L. Risacher7,8, Lori L. Beason‐Held9, Yang An9
and 28 other authorsKonstantinos 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
  1. Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine Nashville Tennessee USA
  2. Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville Tennessee USA
  3. Department of Computer Science Vanderbilt University Nashville Tennessee USA
  4. Department of Electrical and Computer Engineering Vanderbilt University Nashville Tennessee USA
  5. Department of Neurology Vanderbilt University Medical Center Nashville Tennessee USA
  6. Vanderbilt Brain Institute Vanderbilt University Medical Center Nashville Tennessee USA
  7. Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA
  8. Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana USA
  9. Laboratory for Behavioral Neuroscience National Institute on Aging National Institutes of Health Baltimore Maryland USA
  10. Department of Biomedical Engineering Illinois Institute of Technology Chicago Illinois USA
  11. Rush Alzheimer's Disease Center Rush University Medical Center Chicago Illinois USA
  12. Department of Diagnostic Radiology Rush University Medical Center Chicago Illinois USA
  13. Department of Radiology University of Pennsylvania Philadelphia Pennsylvania USA
  14. 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
  15. Department of Radiology and Biomedical Imaging University of California San Francisco California USA
  16. Laboratory of Neuroimaging USC Stevens Institute of Neuroimaging and Informatics Keck School of Medicine University of Southern California Los Angeles California USA
  17. 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
  18. Department of Neurology and Neurological Sciences Stanford University School of Medicine Stanford California USA
  19. Department of Biostatistics Vanderbilt University Medical Center Nashville Tennessee USA
  20. Department of Radiology & Radiological Sciences Vanderbilt University Medical Center Nashville Tennessee USA
  21. Vanderbilt University Medical Center Vanderbilt University Institute of Imaging Science Nashville Tennessee USA
  22. Department of Neurology Johns Hopkins School of Medicine Baltimore Maryland USA
  23. National Alzheimer's Coordinating Center University of Washington Seattle Washington USA
  24. Department of Biomedical Engineering Vanderbilt University Nashville Tennessee USA
  25. Wisconsin Alzheimer's Disease Research Center School of Medicine and Public Health University of Wisconsin Madison Wisconsin USA
  26. Wisconsin Alzheimer's Institute School of Medicine and Public Health University of Wisconsin Madison Wisconsin USA
  27. Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA
Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association, volume 22, issue 7, article e71630
Dates: received 29 January 2026; accepted 18 May 2026; published online 6 July 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/alz.71630 · PMID 42410730 · PMCID PMC13338108 · OpenAlex W4410586290
Open access: hybrid, a free copy (OpenAlex)
Status: code verified
Categories: genetics / omics (modality), structural MRI / diffusion (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, fMRI & imaging
Keywords: Alzheimer's disease, aging, diffusion MRI, GWAS, harmonization, white matter microstructure
MeSH: Aging*, Alzheimer Disease*, Limbic System*, White Matter*, Aged, Aged, 80 and over, Diffusion Magnetic Resonance Imaging, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide (* major topic)
Topic: Dementia and Cognitive Impairment Research (Psychiatry and Mental health, Medicine), according to OpenAlex
Funding: NIH (K01‐EB03289, R01‐EB017230, R01‐AG074339, P30‐AG066515, K01‐AG073584, U24‐AG074855, 75N95D22P00141, R01‐AG059716, UL1‐TR000445, UL1‐TR002243, R01‐AG034962, R01‐AG056534, U19‐AG03655, NIAAG021155, NIAAG027161, NIAAG037639, NIAAG054047, U01AG024904); American Heart Association (26PRE1558066); Alzheimer's Association (IIRG‐08‐88733)
Citations: not cited yet (Europe PMC); 74 references in the paper

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 cell‐adhesion gene. Additional loci were near the KC6, SENP5, RORA, FAM107B, and MIR548A1 genes. In brain tissue, RORA, FAM107B, and KC6 expression was associated with cognition and AD neuropathology. Results converged on insulin and immune biology and shared genetic architecture with lipid and cardiovascular traits.

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.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

Zenodo 13863955

License: CC-BY-4.0
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Size: 69 files
Software Heritage: not checked
Found in: the references
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
  • 27 September 2026: the link answers (HTTP 200)
At the source:

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Data

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Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 48 authors, 6 keywords, 12 MeSH terms, 3 funders, 73 references.

Cite

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://doi.org/10.1002/alz.71630

BibTeX

@article{lorenz2026genetic,
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/alz.71630},
url = {https://doi.org/10.1002/alz.71630},
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 - 2026/07/01
VL - 22
IS - 7
SP - e71630
SN - 1552-5260
PB - Wiley
DO - 10.1002/alz.71630
UR - https://doi.org/10.1002/alz.71630
LA - en
ER -

CSL-JSON

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