amyloid; chemokine factors; complement; endothelial function; microglia; structural equation models; tau; Neurology (clinical); Psychiatry and Mental Health
Abstract :
[en] [en] INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum.
METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid.
RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline.
DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.
Disciplines :
Neurology
Author, co-author :
Teipel, Stefan J ; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock Germany ; Department of Psychosomatic Medicine University of Rostock Rostock Germany
Dyrba, Martin; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock Germany
Kleineidam, Luca; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany
Brosseron, Frederic; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany
Levin, Fedor; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock Germany
Bruno, Davide; School of Psychology Liverpool John Moores University Liverpool UK
Buerger, Katharina; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Munich Germany ; Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich Munich Germany
Cosma, Nicoleta; Charité - Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany
Schneider, Luisa-Sophie; Charité - Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany
Düzel, Emrah; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Magdeburg Germany ; Institute of Cognitive Neurology and Dementia Research (IKND) Otto-von-Guericke University Magdeburg Germany
Glanz, Wenzel; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Magdeburg Germany
Fliessbach, Klaus; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany
Janowitz, Daniel; Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich Munich Germany
Kilimann, Ingo; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock Germany ; Department of Psychosomatic Medicine University of Rostock Rostock Germany
Laske, Christoph; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Tübingen Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy University of Tübingen Tübingen Germany
Munk, Matthias H; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Tübingen Germany ; Department of Psychiatry and Psychotherapy University of Tübingen Tübingen Germany
Maier, Franziska; Department of Psychiatry University of Cologne Cologne Germany
Peters, Oliver; Charité - Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany ; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Berlin Germany
Pomara, Nunzio; Nathan Kline Institute for Psychiatric Research Orangeburg New York USA ; Department of Psychiatry School of Medicine New York University New York New York USA
Perneczky, Robert; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Munich Germany ; Department of Psychiatry and Psychotherapy University Hospital LMU Munich Munich Germany ; Munich Cluster for Systems Neurology (SyNergy) Munich Munich Germany ; Ageing Epidemiology Research Unit (AGE), School of Public Health Imperial College London London UK
Rauchmann, Boris-Stephan; Department of Psychiatry and Psychotherapy University Hospital LMU Munich Munich Germany
Priller, Josef; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Berlin Germany ; Department of Psychiatry and Psychotherapy Charité Berlin Berlin Germany ; Department of Psychiatry and Psychotherapy Technical University of Munich Munich Germany ; University of Edinburgh and UK DRI Edinburgh UK
Ramirez, Alfredo; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany ; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne Cologne Germany ; Division of Neurogenetics and Molecular Psychiatry Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany ; Department of Psychiatry and Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases San Antonio Texas USA
Roy, Nina; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany
Schneider, Anja; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany
Spottke, Annika; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurology University of Bonn Bonn Germany
Spruth, Eike J; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Berlin Germany ; Department of Psychiatry and Psychotherapy Charité Berlin Berlin Germany
Roeske, Sandra; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany
Wagner, Michael; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany
Wiltfang, Jens; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Goettingen Germany ; Department of Psychiatry and Psychotherapy University Medical Center Goettingen, University of Goettingen Goettingen Germany ; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED) Department of Medical Sciences University of Aveiro Aveiro Portugal
Wolfsgruber, Steffen; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany
Bartels, Claudia; Department of Psychiatry and Psychotherapy University Medical Center Goettingen, University of Goettingen Goettingen Germany
Jessen, Frank; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Psychiatry University of Cologne Cologne Germany ; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne Cologne Germany
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) ; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn Germany ; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany
DELCODE study group and the Alzheimer´s Disease Neuroimaging Initiative
The work was supported by a grant to S.J.T. within the CureDem funding of the Federal Ministry of Research (BMBF), grant number 01KX2130, and additionally by a grant from the German Research Council (DFG), grant number 390873048 (Cluster of Excellence EXC 2151 \u201CImmunosensation\u201D) to M.T.H.
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