Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition.

Autor: Hayek D; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany., Ziegler G; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany., Kleineidam L; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Brosseron F; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Neurology, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany., Nemali A; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany., Vockert N; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany., Ravichandran KA; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Neurology, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany., Betts MJ; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany., Peters O; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute of Psychiatry and Neuroscience, Hindenburgdamm 30, 12203, Berlin, Germany.; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany., Schneider LS; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute of Psychiatry and Neuroscience, Hindenburgdamm 30, 12203, Berlin, Germany., Wang X; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute of Psychiatry and Neuroscience, Hindenburgdamm 30, 12203, Berlin, Germany., Priller J; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117, Berlin, Germany.; School of Medicine, Technical University of Munich; Department of Psychiatry and Psychotherapy, Munich, Germany.; University of Edinburgh and UK DRI, Edinburgh, UK., Altenstein S; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117, Berlin, Germany., Schneider A; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Fliessbach K; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Wiltfang J; German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, Göttingen, 37075, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, University of Göttingen, Von-Siebold-Str. 5, 37075, Göttingen, Germany.; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal., Bartels C; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, University of Göttingen, Von-Siebold-Str. 5, 37075, Göttingen, Germany., Rostamzadeh A; Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924, Cologne, Germany., Glanz W; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany., Buerger K; German Center for Neurodegenerative Diseases (DZNE, Munich), Feodor-Lynen-Strasse 17, 81377, Munich, Germany.; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Feodor-Lynen-Strasse 17, 81377, Munich, Germany., Janowitz D; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Feodor-Lynen-Strasse 17, 81377, Munich, Germany., Perneczky R; German Center for Neurodegenerative Diseases (DZNE, Munich), Feodor-Lynen-Strasse 17, 81377, 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 BS; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.; Department of Neuroradiology, University Hospital LMU, Munich, Germany., Teipel S; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.; Department of Psychosomatic Medicine, Rostock University Medical Center, Gehlsheimer Str. 20, 18147, Rostock, Germany., Kilimann I; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.; Department of Psychosomatic Medicine, Rostock University Medical Center, Gehlsheimer Str. 20, 18147, Rostock, Germany., Laske C; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany., Mengel D; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.; Division Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany., Synofzik M; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.; Division Translational Genomics of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany., Munk MH; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.; Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany., Spottke A; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; Department of Neurology, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Roy N; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Roeske S; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Kuhn E; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Ramirez A; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931, Köln, 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 & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA., Dobisch L; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany., Schmid M; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; Institute for Medical Biometry, University Hospital Bonn, Venusberg-Campus 1, D-53127, Bonn, Germany., Berger M; Institute for Medical Biometry, University Hospital Bonn, Venusberg-Campus 1, D-53127, Bonn, Germany., Wolfsgruber S; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Yakupov R; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany., Hetzer S; Berlin Center for Advanced Neuroimaging, Charité - Universitätsmedizin Berlin, Berlin, Germany., Dechent P; MR-Research in Neurosciences, Department of Cognitive Neurology, Georg-August-University Goettingen, Goettingen, Germany., Ewers M; German Center for Neurodegenerative Diseases (DZNE, Munich), Feodor-Lynen-Strasse 17, 81377, Munich, Germany., Scheffler K; Department for Biomedical Magnetic Resonance, University of Tübingen, 72076, Tübingen, Germany., Schott BH; German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, Göttingen, 37075, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, University of Göttingen, Von-Siebold-Str. 5, 37075, Göttingen, Germany.; Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany.; Center for Behavioral Brain Sciences, Magdeburg, Germany., Schreiber S; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany.; Center for Behavioral Brain Sciences, Magdeburg, Germany.; Department of Neurology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany., Orellana A; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., de Rojas I; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Marquié M; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Boada M; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Sotolongo O; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., González PG; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain., Puerta R; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain., Düzel E; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.; Center for Behavioral Brain Sciences, Magdeburg, Germany., Jessen F; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931, Köln, Germany., Wagner M; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Ruiz A; Research Center and Memory Clinic. Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Heneka MT; German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Neurology, University of Bonn Medical Center, Venusberg-Campus 1, 53127, Bonn, Germany.; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 avenue des Hauts Fourneaux, 4362, Esch-sur- Alzette, Luxembourg.; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA, 01655, USA., Maass A; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, Magdeburg, 39120, Germany. anne.maass@dzne.de.; Center for Behavioral Brain Sciences, Magdeburg, Germany. anne.maass@dzne.de.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Apr; Vol. 29 (4), pp. 992-1004. Date of Electronic Publication: 2024 Jan 12.
DOI: 10.1038/s41380-023-02387-3
Abstrakt: Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aβ42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM; n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological Aβ when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic clearance, other markers might rather reflect proinflammatory states that have detrimental impact on brain integrity.
(© 2024. The Author(s).)
Databáze: MEDLINE
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