Communications Biology (Nov 2023)
Identification of circulating proteins associated with general cognitive function among middle-aged and older adults
- Adrienne Tin,
- Alison E. Fohner,
- Qiong Yang,
- Jennifer A. Brody,
- Gail Davies,
- Jie Yao,
- Dan Liu,
- Ilana Caro,
- Joni V. Lindbohm,
- Michael R. Duggan,
- Osorio Meirelles,
- Sarah E. Harris,
- Valborg Gudmundsdottir,
- Adele M. Taylor,
- Albert Henry,
- Alexa S. Beiser,
- Ali Shojaie,
- Annabell Coors,
- Annette L. Fitzpatrick,
- Claudia Langenberg,
- Claudia L. Satizabal,
- Colleen M. Sitlani,
- Eleanor Wheeler,
- Elliot M. Tucker-Drob,
- Jan Bressler,
- Josef Coresh,
- Joshua C. Bis,
- Julián Candia,
- Lori L. Jennings,
- Maik Pietzner,
- Mark Lathrop,
- Oscar L. Lopez,
- Paul Redmond,
- Robert E. Gerszten,
- Stephen S. Rich,
- Susan R. Heckbert,
- Thomas R. Austin,
- Timothy M. Hughes,
- Toshiko Tanaka,
- Valur Emilsson,
- Ramachandran S. Vasan,
- Xiuqing Guo,
- Yineng Zhu,
- Christophe Tzourio,
- Jerome I. Rotter,
- Keenan A. Walker,
- Luigi Ferrucci,
- Mika Kivimäki,
- Monique M. B. Breteler,
- Simon R. Cox,
- Stephanie Debette,
- Thomas H. Mosley,
- Vilmundur G. Gudnason,
- Lenore J. Launer,
- Bruce M. Psaty,
- Sudha Seshadri,
- Myriam Fornage
Affiliations
- Adrienne Tin
- Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center
- Alison E. Fohner
- Department of Epidemiology, University of Washington
- Qiong Yang
- Department of Biostatistics, Boston University
- Jennifer A. Brody
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Gail Davies
- Lothian Birth Cohorts, Department of Psychology, University of Edinburgh
- Jie Yao
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Dan Liu
- Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
- Ilana Caro
- University of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
- Joni V. Lindbohm
- Broad Institute of the Massachusetts Institute of Technology and Harvard University, The Klarman Cell Observatory
- Michael R. Duggan
- Laboratory of Behavioral Neuroscience, National Institute on Aging
- Osorio Meirelles
- National Institute on Aging, National Institutes of Health, Laboratory of Epidemiology and Population Science
- Sarah E. Harris
- Lothian Birth Cohorts, Department of Psychology, University of Edinburgh
- Valborg Gudmundsdottir
- Faculty of Medicine, University of Iceland
- Adele M. Taylor
- Lothian Birth Cohorts, Department of Psychology, University of Edinburgh
- Albert Henry
- Institute of Cardiovascular Science, University of London
- Alexa S. Beiser
- Department of Biostatistics, Boston University
- Ali Shojaie
- Department of Biostatistics, University of Washington
- Annabell Coors
- Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
- Annette L. Fitzpatrick
- Department of Epidemiology, University of Washington
- Claudia Langenberg
- Precision Healthcare Institute, Queen Mary University of London
- Claudia L. Satizabal
- Framingham Heart Study
- Colleen M. Sitlani
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Eleanor Wheeler
- MRC Epidemiology Unit, University of Cambridge
- Elliot M. Tucker-Drob
- Department of Psychology, University of Texas
- Jan Bressler
- Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston
- Josef Coresh
- Johns Hopkins University
- Joshua C. Bis
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Julián Candia
- Translational Gerontology Branch, National Institute on Aging
- Lori L. Jennings
- Novartis Institutes for Biomedical Research
- Maik Pietzner
- Precision Healthcare Institute, Queen Mary University of London
- Mark Lathrop
- McGill Genome Centre
- Oscar L. Lopez
- Departments of Neurology and Psychiatry, University of Pittsburgh
- Paul Redmond
- Lothian Birth Cohorts, Department of Psychology, University of Edinburgh
- Robert E. Gerszten
- Department of Medicine, Beth Israel Deaconess Medical Center
- Stephen S. Rich
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia
- Susan R. Heckbert
- Department of Epidemiology, University of Washington
- Thomas R. Austin
- Department of Epidemiology, University of Washington
- Timothy M. Hughes
- Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine
- Toshiko Tanaka
- Translational Gerontology Branch, National Institute on Aging
- Valur Emilsson
- Faculty of Medicine, University of Iceland
- Ramachandran S. Vasan
- Framingham Heart Study
- Xiuqing Guo
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Yineng Zhu
- Department of Biostatistics, Boston University
- Christophe Tzourio
- University of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Keenan A. Walker
- Laboratory of Behavioral Neuroscience, National Institute on Aging
- Luigi Ferrucci
- Translational Gerontology Branch, National Institute on Aging
- Mika Kivimäki
- UCL Brain Sciences, University College London
- Monique M. B. Breteler
- Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
- Simon R. Cox
- Lothian Birth Cohorts, Department of Psychology, University of Edinburgh
- Stephanie Debette
- University of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
- Thomas H. Mosley
- Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center
- Vilmundur G. Gudnason
- Faculty of Medicine, University of Iceland
- Lenore J. Launer
- Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health
- Bruce M. Psaty
- Department of Epidemiology, University of Washington
- Sudha Seshadri
- Framingham Heart Study
- Myriam Fornage
- Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston
- DOI
- https://doi.org/10.1038/s42003-023-05454-1
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 1 – 14
Abstract
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.
