Evidence mapPaperPMID 39011113Full record

ArticleResearch square2024

Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.

Stephanie Debette, Ilana Caro, Daniel Western, Shinichi Namba, Na Sun, Shuji Kawaguchi, Yunye He, Masashi Fujita, Gennady Roshchupkin, Tim D'Aoust and 47 more

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In one paragraph

Article in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

57 authors.

Stephanie DebetteUniversity of Bordeaux.ORCID 0000-0001-8675-7968
Ilana CaroUniversity of Bordeaux.ORCID 0000-0003-3075-4682
Daniel WesternDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-3725-9553
Shinichi NambaOsaka University.ORCID 0000-0002-7486-3146
Na SunMIT Computer Science and Artificial Intelligence Laboratory; Broad Institute of MIT and Harvard.
Shuji KawaguchiKyoto University Graduate School of Medicine.
Yunye HeGraduate School of Frontier Sciences, The University of Tokyo.
Masashi FujitaColumbia University Irving Medical Center.
Gennady RoshchupkinErasmus Medical Center.ORCID 0000-0002-3403-2313
Tim D'AoustBordeaux Population Health, Inserm U1219, University of Bordeaux.
Marie-Gabrielle DuperronUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219.ORCID 0000-0001-7408-7792
Murali SargurupremrajUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, F-33000 Bordeaux, France; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases Unive.
Masaru KoidoGraduate School of Frontier Sciences, The University of Tokyo.ORCID 0000-0002-0348-0666
Marziehsadat AhmadiVictor Phillip Dahdaleh Institute of Genomic Medicine, McGill University.
Chengran YangWashington University in St. Louis.ORCID 0000-0003-4577-5590
Jigyasha TimsinaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Laura IbanezWashington University in St. Louis.
Koichi MatsudaDepartment of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo.
Yutaka SuzukiThe University of Tokyo.ORCID 0000-0003-4852-1879
Yoshiya OdaGraduate School of Medicine, The University of Tokyo.
Akinori KanaiThe University of Tokyo.ORCID 0000-0003-1555-6768
Hans Markus MunterMcGill University.ORCID 0000-0002-3165-2840
Dan AuldVictor Phillip Dahdaleh Institute of Genomic Medicine, McGill University.ORCID 0000-0002-9486-1105
Iana AstafevaBordeaux Population Health, Inserm U1219, University of Bordeaux; Institute of Neurodegenerative Diseases.
Raquel PuertaAce Alzheimer Center Barcelona.ORCID 0000-0002-1191-5893
Jerome RotterThe Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center.ORCID 0000-0001-7191-1723
Bruce PsatyCardiovascular Health Research Unit.ORCID 0000-0002-7278-2190
Joshua BisUniversity of Washington.ORCID 0000-0002-3409-1110
Will LongstrethUniversity of Washington.
Thierry CouffinhalUniversity of Bordeaux, The clinical unit of Exploration, Prevention and Care Center for Atherosclerosis (CEPTA), CHUB, Inserm U1034.ORCID 0000-0002-9217-2533
Pablo Garcia-GonzalezAce Alzheimer Center Barcelona.ORCID 0000-0003-0125-5403
Vanesa PytelAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III.
Marta MarquiéACE Alzheimer Center Barcelona.ORCID 0000-0002-0660-0950
Amanda CanoAce Alzheimer Center Barcelona.
Mercè BoadaUniversitat Internacional de Catalunya.ORCID 0000-0003-2617-3009
Marc JoliotGIN, IMN/UMR5293 UB/CNRS/CEA.ORCID 0000-0001-7792-308X
Mark LathropDepartment of Human Genetics, McGill University, 1205 Dr Penfield Avenue, Montreal, QC, H3A 1B1, Canada.
Quentin Le GrandUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219.ORCID 0000-0002-9299-0747
Lenore LaunerNational Institute on Aging, National Institutes of Health.ORCID 0000-0002-3238-7612
Joanna WardlawUniversity of Edinburgh.ORCID 0000-0002-9812-6642
Myriam HeimanMassachusetts Institute of Technology.ORCID 0000-0002-6365-8673
Agustin RuizGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center; Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya;CIBERN.
Paul MatthewsUK Dementia Research Institute Centre at Imperial College London.ORCID 0000-0002-1619-8328
Sudha SeshadriUniversity of Texas Health Science Center.ORCID 0000-0001-6135-2622
Myriam Fornage1. Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center 2. Human Genetics Center, Department of Epidemiology, School of Public Health.ORCID 0000-0003-0677-8158
Hieab AdamsDepartment of Human Genetics, Radboud University Medical Center; Latin American Brain Health (BrainLat), Universidad Adolfo Ibáñez.
Aniket MishraUniversity of Bordeaux.ORCID 0000-0002-8141-1543
David-Alexandre TrégouëtINSERM.ORCID 0000-0001-9084-7800
Yukinori OkadaDepartment of Genome Informatics, Graduate School of Medicine, The Univ. of Tokyo; Department of Statistical Genetics, Osaka Univ. Graduate School of Medicine; Laboratory for Systems Genetic, RIKEN.
Manolis KellisMIT.ORCID 0000-0001-7113-9630
Philip De JagerColumbia University Irving Medical Center.ORCID 0000-0002-8057-2505
Christophe TzourioORCID 0000-0002-6517-2984
Yoichiro KamataniThe University of Tokyo.ORCID 0000-0001-8748-5597
Fumihiko MatsudaKyoto University Graduate School of Medicine.
Carlos CruchagaWashington University.ORCID 0000-0002-0276-2899

Funding

PREDICTING COGNITIVE DECLINE IN NONDEMENTED ELDER SUBJECTSP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2023
$14.7M
Tau Burden and Spatial Spread in Preclinical Alzheimer DiseaseP01AG026276 · WASHINGTON UNIVERSITY · 2005 to 2025
$5.2M
Research Education ComponentP30AG066444 · WASHINGTON UNIVERSITY · 2025 to 2025
$4.4M
Stanford Alzheimer's Disease Research CenterP30AG066515 · STANFORD UNIVERSITY · 2025 to 2025
$4.3M
Exceptional aging: 12 year trajectories to functionR01AG023629 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2004 to 2005
$2.6M
CHS Events Follow-up StudyU01HL080295 · UNIVERSITY OF WASHINGTON · 2005 to 2005
$1.1M
ALZHEIMERS RESEARCH PROJECT: Genetic Markers of Brain AgingZIAAG007270 · NATIONAL INSTITUTE ON AGING · 2025 to 2025
$109k
CENTRAL BLOOD ANALYSIS LABORATORY FOR CHSN01HC085086 · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · 1988 to 2000
CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84N01HC085083 · UNIVERSITY OF CALIFORNIA DAVIS · 1988 to 1999
CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84N01HC085082 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1988 to 2000
CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84N01HC085081 · JOHNS HOPKINS UNIVERSITY · 1988 to 2000
CORONARY HEART DISEASE &STROKE IN THE ELDERLYN01HC085080 · WAKE FOREST UNIVERSITY · 1988 to 2000
NHLBI 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 U01 HL080295NHLBI NIH HHS U01 HL130114NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066515NIA NIH HHS R00 AG062723NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG044546NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007NIA NIH HHS U01 AG058922
6 · The paper itself

Abstract

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific mechanism-based treatment. We used Mendelian randomization to combine a unique cerebrospinal fluid (CSF) and plasma pQTL resource with the latest European-ancestry GWAS of MRI-markers of cSVD (white matter hyperintensities, perivascular spaces). We describe a new biological fingerprint of 49 protein-cSVD associations, predominantly in the CSF. We implemented a multipronged follow-up, across fluids, platforms, and ancestries (Europeans and East-Asian), including testing associations of direct plasma protein measurements with MRI-cSVD. We highlight 16 proteins robustly associated in both CSF and plasma, with 24/4 proteins identified in CSF/plasma only. cSVD-proteins were enriched in extracellular matrix and immune response pathways, and in genes enriched in microglia and specific microglial states (integration with single-nucleus RNA sequencing). Immune-related proteins were associated with MRI-cSVD already at age twenty. Half of cSVD-proteins were associated with stroke, dementia, or both, and seven cSVD-proteins are targets for known drugs (used for other indications in directions compatible with beneficial therapeutic effects. This first cSVD proteogenomic signature opens new avenues for biomarker and therapeutic developments.

Identifiers

PMID39011113
PMCPMC11247936

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.