ArticleCommunications biology2023
Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.
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Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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17citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% of its field
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty.Nature aging · 2025Pooled it
- Genetic Prioritization of Plasma Proteins Across Dementia Subtypes: A Proteome-Wide Mendelian Randomization and Bayesian Colocalization Analysis.Cellular and molecular neurobiology · 2026Article
- Plasma proteomics improves thrombosis prediction in patients with cancer and identifies targetable IL-17-driven endothelial activation.Science translational medicine · 2026Article
- Proteomic polygenic risk scores of age-related plasma protein levels reveal a role for Metalloproteinase inhibitor 2 (TIMP2) in cognitive performance.Neurobiology of aging · 2026Article
- The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer's Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression.Molecular neurobiology · 2025Review
- Plasma profiles of neurology-related proteins in at-risk mental state and first-episode psychosis: Associations with psychotic symptoms and cognitive performance.Brain, behavior, & immunity - health · 2025Article
- Integrated Multi-Omics Analysis and Cross-Model Validation Reveal Mitochondrial Signatures in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Article
- Profiling 92 circulating neurobiological proteins identifies novel candidate biomarkers of long-term cognitive outcome after ischemic stroke.Scientific reports · 2025Article
- Plasma proteomic analysis of intermuscular fat links muscle integrity with processing speed in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Novel Dietary Inflammatory Score and Risk of Incident CKD.Clinical journal of the American Society of Nephrology : CJASN · 2025Article
- Genomic Characterisation of the Relationship and Causal Links Between Vascular Calcification, Alzheimer's Disease, and Cognitive Traits.Biomedicines · 2025Article
- SomaScan Bioinformatics: Normalization, Quality Control, and Assessment of Pre-Analytical Variation.Methods in molecular biology (Clifton, N.J.) · 2025Review
- β2-microglobulin and cognitive decline: unraveling the mediating role of the Dunedin Pace of Aging methylation.Frontiers in aging neuroscience · 2025Article
- Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses.Translational psychiatry · 2024Article
- Special Issue "Deployment of Proteomics Approaches in Biomedical Research".International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
57 authors at 20 institutions in 7 countries.
Adrienne Tin *Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA. atin@umc.edu.ORCID 0000-0002-4207-5866
Alison E Fohner *Department of Epidemiology, University of Washington, Seattle, WA, USA. afohner@uw.edu.ORCID 0000-0003-4231-3331
Qiong YangDepartment of Biostatistics, Boston University, Boston, MA, USA.ORCID 0000-0002-3658-1375
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Gail DaviesLothian Birth Cohorts, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.ORCID 0000-0003-1120-7026
Jie YaoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Dan LiuPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Ilana CaroUniversity of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, Bordeaux, France.ORCID 0000-0003-3075-4682
Joni V LindbohmBroad Institute of the Massachusetts Institute of Technology and Harvard University, The Klarman Cell Observatory, Cambridge, MA, USA.
Michael R DugganLaboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.ORCID 0000-0002-1029-4423
Osorio MeirellesNational Institute on Aging, National Institutes of Health, Laboratory of Epidemiology and Population Science, Bethesda, MD, USA.
Sarah E HarrisLothian Birth Cohorts, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.ORCID 0000-0002-4941-5106
Valborg GudmundsdottirFaculty of Medicine, University of Iceland, Reykjavik, Iceland.
Adele M TaylorLothian Birth Cohorts, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
Albert HenryInstitute of Cardiovascular Science, University of London, London, UK.
Alexa S BeiserDepartment of Biostatistics, Boston University, Boston, MA, USA.
Ali ShojaieDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Annabell CoorsPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID 0000-0001-9000-6390
Annette L FitzpatrickDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Claudia LangenbergPrecision Healthcare Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-5017-7344
Claudia L SatizabalFramingham Heart Study, Framingham, MA, USA.
Colleen M SitlaniCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Eleanor WheelerMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Elliot M Tucker-DrobDepartment of Psychology, University of Texas, Austin, TX, USA.ORCID 0000-0001-5599-6237
Jan BresslerHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0001-6578-4772
Josef CoreshJohns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-4598-0669
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-3409-1110
Julián CandiaTranslational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.ORCID 0000-0001-5793-8989
Lori L JenningsNovartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA, USA.ORCID 0000-0001-5130-8417
Maik PietznerPrecision Healthcare Institute, Queen Mary University of London, London, UK.ORCID 0000-0003-3437-9963
Mark LathropMcGill Genome Centre, Montreal, QC, Canada.
Oscar L LopezDepartments of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-8546-8256
Paul RedmondLothian Birth Cohorts, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
Robert E GersztenDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID 0000-0002-6767-7687
Stephen S RichCenter for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0003-3872-7793
Susan R HeckbertDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7100-512X
Thomas R AustinDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Timothy M HughesDepartment of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Toshiko TanakaTranslational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Valur EmilssonFaculty of Medicine, University of Iceland, Reykjavik, Iceland.ORCID 0000-0001-9982-0524
Ramachandran S VasanFramingham Heart Study, Framingham, MA, USA.
Xiuqing GuoThe 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 0000-0002-5264-5068
Yineng ZhuDepartment of Biostatistics, Boston University, Boston, MA, USA.
Christophe TzourioUniversity of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, Bordeaux, France.
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 0000-0001-7191-1723
Keenan A WalkerLaboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.ORCID 0000-0002-5989-9853
Luigi FerrucciTranslational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.ORCID 0000-0002-6273-1613
Mika KivimäkiUCL Brain Sciences, University College London, London, UK.ORCID 0000-0002-4699-5627
Monique M B BretelerPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID 0000-0002-0626-9305
Simon R CoxLothian Birth Cohorts, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.ORCID 0000-0003-4036-3642
Stephanie DebetteUniversity of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, Bordeaux, France.ORCID 0000-0001-8675-7968
Thomas H MosleyMemory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA.
Vilmundur G GudnasonFaculty of Medicine, University of Iceland, Reykjavik, Iceland.ORCID 0000-0001-5696-0084
Lenore J LaunerLaboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0002-3238-7612
Bruce M PsatyDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7278-2190
Sudha SeshadriFramingham Heart Study, Framingham, MA, USA.ORCID 0000-0001-6135-2622
Myriam FornageHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0003-0677-8158
University of Washington · USNational Institute on Aging · USUniversity of Edinburgh · GBBoston University · USUCLA Medical Center · USUniversité de Bordeaux · FRUniversity of Iceland · ISGerman Center for Neurodegenerative Diseases · DEJohns Hopkins University · USNational Institutes of Health · USQueen Mary University of London · GBThe University of Texas Health Science Center at Houston · USBeth Israel Deaconess Medical Center · USBroad Institute · USInstitute for Neurodegenerative Disorders · USMcGill Genome Centre · CAThe University of Texas at Austin · USThe University of Texas Health Science Center at San Antonio · USUniversity of Bonn · DEUniversity of Cambridge · GB
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MSubclinical Vascular Contributions to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis (MESA) Multisite Study of AD (Renewal)R01AG058969 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Timothy M. Hughes, YONGMEI LIU · 2018 to 2026
$33.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MFRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8MUniversity of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI ALI SHOJAIE · 2020 to 2026
$29.0MBuilding on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MWake Forest University School of Medicine Alzheimer's Disease Research CenterP30AG072947 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SUZANNE CRAFT · 2021 to 2026
$24.3MBiotechnology and Biological Sciences Research Council BB/F019394/1Chief Scientist OfficeMedical Research Council MC_UU_00006/1Medical Research Council MR/R024227/1Medical Research Council MR/S011676/1NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS 75N92021D00006NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005CNHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800003INHLBI NIH HHS HHSN268201800004INHLBI NIH HHS HHSN268201800005INHLBI NIH HHS HHSN268201800006INHLBI NIH HHS HHSN268201800007INHLBI NIH HHS N01 HC025195NHLBI 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 N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL131136NHLBI NIH HHS R01 HL132320NHLBI NIH HHS R01 HL144483NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NHLBI NIH HHS U01 HL130114NIA NIH HHS K01 AG071689NIA NIH HHS N01 AG012100NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072947NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG025941NIA NIH HHS R01 AG026307NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG054628NIA NIH HHS R01 AG056477NIA NIH HHS R01 AG058969NIA NIH HHS R01 AG065596NIA NIH HHS R01 AG066524NIA NIH HHS R01 AG068629NIA NIH HHS RF1 AG059421NIA NIH HHS RF1 AG063507NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG058589NIDA NIH HHS HHSN271201200022CNIDDK NIH HHS P30 DK063491NINDS NIH HHS R01 NS087541NINDS NIH HHS UF1 NS125513NINDS NIH HHS UH2 NS100605NINDS NIH HHS UH3 NS100605
Abstract
Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.
Indexed as
Alzheimer DiseaseCognitive DysfunctionAgedBiomarkersCognitionHumansMiddle AgedNeuronsBiomarkers
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