ArticleNature aging2025
Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.
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Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7citing papers in PubMed
–field-weighted citation impact
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Who cites it
7 citing papers in PubMed.
- Genome-wide association study identifies toll-like receptor four protein-mediated metabolic remodelling affecting gout pathogenesis.Journal of global health · 2026Observational
- Whole-exome sequencing identifies matrisomal gene associations in monogenic cerebral small vessel disease.Journal of neurology · 2026Article
- Multiomics Profiling Supports Cathepsin B as a Protective Factor in Cerebral Small Vessel Disease.Research square · 2026Article
- Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins.medRxiv : the preprint server for health sciences · 2026Article
- Neuroinflammation and blood-brain barrier dysfunction in cerebral small vessel disease: mechanisms, biomarkers, and therapeutic implications.European journal of medical research · 2026Review
- Cross-ancestry comparison of aptamer and antibody protein measures.Nature communications · 2026Article
- The international society of vascular behavioural and cognitive disorders: highlights from VasCog 2025 in the UK.Cerebral circulation - cognition and behavior · 2026Article
Corrections and comments
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Authors and funding
57 authors.
Ilana Caro *Bordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0003-3075-4682
Daniel Western *Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-3725-9553
Shinichi Namba *Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-7486-3146
Na SunMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA.
Shuji KawaguchiCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0002-4045-6518
Yunye HeGraduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-8581-7826
Masashi FujitaDepartment of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, New York, NY, USA.
Gennady RoshchupkinDepartment of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Tim D'AoustBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.
Marie-Gabrielle DuperronBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.
Muralidharan SargurupremrajGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.ORCID http://orcid.org/0000-0003-1684-3750
Ami TsuchidaBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.
Masaru KoidoGraduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-0348-0666
Marziehsadat AhmadiVictor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada.
Chengran YangDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-4577-5590
Jigyasha TimsinaDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-4794-9187
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Koichi MatsudaGraduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Yutaka SuzukiGraduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0003-4852-1879
Yoshiya OdaGraduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Akinori KanaiGraduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Pouria JandaghiVictor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada.
Markus MunterVictor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada.
Daniel AuldVictor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-9486-1105
Iana AstafevaBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.
Raquel PuertaAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0002-1191-5893
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3409-1110
W T LongstrethDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Thierry CouffinhalInserm U1034, Biologie Des Maladies Cardiovasculaires, Université de Bordeaux, Bordeaux, France.
Pablo García-GonzálezAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-0125-5403
Vanesa PytelAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Marta MarquiéAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0002-0660-0950
Amanda CanoAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Mercè BoadaAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2617-3009
Marc JoliotInstitut des Maladies Neurodégénératives, IMN-UMR5293, Université de Bordeaux, CNRS, CEA, Bordeaux, France.ORCID http://orcid.org/0000-0001-7792-308X
Mark LathropVictor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada.
Quentin Le GrandBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0002-9299-0747
Lenore J LaunerIntramural Research Program, National Institue on Aging, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-3238-7612
Joanna M WardlawCentre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, Edinburgh, UK.ORCID http://orcid.org/0000-0002-9812-6642
Myriam HeimanDepartment of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Agustin RuizGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.ORCID http://orcid.org/0000-0003-2633-2495
Paul M MatthewsDepartment of Brain Sciences, Imperial College, London, UK.
Sudha SeshadriGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-6135-2622
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0003-0677-8158
Hieab AdamsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Aniket MishraBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.
David-Alexandre TrégouëtBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0001-9084-7800
Yukinori OkadaDepartment of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-0311-8472
Manolis KellisMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7113-9630
Philip L De JagerDepartment of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-8057-2505
Christophe TzourioBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0002-6517-2984
Yoichiro KamataniGraduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-8748-5597
Fumihiko MatsudaCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. cruchagac@wustl.edu.ORCID http://orcid.org/0000-0002-0276-2899
Stéphanie DebetteBordeaux Population Health Research Center, Inserm U1219, Université de Bordeaux, Bordeaux, France. stephanie.debette@inserm.fr.ORCID http://orcid.org/0000-0001-8675-7968
Funding
PREDICTING COGNITIVE DECLINE IN NONDEMENTED ELDER SUBJECTSP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2023
$14.7MUCLA Clinical and Translational Science InstituteUL1TR001881 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$9.9MPilot & Feasibility ProgramP30DK063491 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2003 to 2025
$5.4MTau Burden and Spatial Spread in Preclinical Alzheimer DiseaseP01AG026276 · WASHINGTON UNIVERSITY · 2005 to 2025
$5.2MResearch Education ComponentP30AG066444 · WASHINGTON UNIVERSITY · 2025 to 2025
$4.4MSouth Texas Alzheimer's Disease Center Research and Education CoreP30AG066546 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$2.9MExceptional aging: 12 year trajectories to functionR01AG023629 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2004 to 2005
$2.6MInfrastructure for mentored access to CHS data and specimensR01HL172803 · UNIVERSITY OF WASHINGTON · 2025 to 2025
$1.4MCHS Events Follow-up StudyU01HL080295 · UNIVERSITY OF WASHINGTON · 2005 to 2005
$1.1MSingle-cell multi-region transcriptional and epigenomic dissection of VCID.R01NS129032 · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2025 to 2025
$1.0MCORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84N01HC085082 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1988 to 2000
–CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65 TO 84N01HC085079 · UNIVERSITY OF WASHINGTON · 1988 to 2005
–Agence Nationale de la Recherche (French National Research Agency) ANR-18-RHUS-0002, ANR-10-COHO-05NCATS NIH HHS UL1 TR001881NHLBI NIH HHS 75N92021D00006NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL172803NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL130114NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG059305NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066546NIA NIH HHS R00 AG062723NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG059421NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG059421NIA NIH HHS RF1 AG063507NIA NIH HHS RF1 AG074007NIA NIH HHS U01 AG058922NIDDK NIH HHS P30 DK063491NINDS NIH HHS R01 NS129032NINDS NIH HHS RF1 NS129032U.S. Department of Health Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health) R01NS129032
Abstract
Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences between fluids. The proteins are enriched in pathways related to the extracellular matrix, immune response and microglial activity. Many also associate with stroke and dementia, and several correspond to existing drug targets. Together, these findings reveal a robust biological fingerprint of cSVD and highlight opportunities for biomarker and drug discovery and repositioning.
Indexed as
Cerebral Small Vessel DiseasesProteogenomicsAgedBiomarkersFemaleHumansMagnetic Resonance ImagingMaleMendelian Randomization AnalysisBiomarkers
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