Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology.

Autor: Blömeke L; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany.; attyloid GmbH Düsseldorf Germany.; Institut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf Düsseldorf Germany., Rehn F; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany.; attyloid GmbH Düsseldorf Germany.; Institut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf Düsseldorf Germany., Kraemer-Schulien V; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany., Kutzsche J; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany., Pils M; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany.; attyloid GmbH Düsseldorf Germany.; Institut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf Düsseldorf Germany., Bujnicki T; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany., Lewczuk P; Department of Psychiatry and Psychotherapy Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg Erlangen Germany., Kornhuber J; Department of Psychiatry and Psychotherapy Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg Erlangen Germany., Freiesleben SD; Department of Psychiatry and Psychotherapy Charité Berlin Germany.; German Center for Neurodegenerative Diseases (DZNE) Berlin Germany., Schneider LS; Department of Psychiatry and Psychotherapy Charité Berlin Germany., Preis L; Department of Psychiatry and Psychotherapy Charité Berlin Germany., Priller J; Department of Psychiatry and Psychotherapy Charité Berlin Germany.; German Center for Neurodegenerative Diseases (DZNE) Berlin Germany.; School of Medicine Department of Psychiatry and Psychotherapy Technical University of Munich Munich Germany.; University of Edinburgh and UK DRI Edinburgh UK., Spruth EJ; Department of Psychiatry and Psychotherapy Charité Berlin Germany.; German Center for Neurodegenerative Diseases (DZNE) Berlin Germany., Altenstein S; Department of Psychiatry and Psychotherapy Charité Berlin Germany.; German Center for Neurodegenerative Diseases (DZNE) Berlin Germany., Lohse A; Department of Psychiatry and Psychotherapy Charité Berlin Germany., Schneider A; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany., Fliessbach K; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany., Wiltfang J; German Center for Neurodegenerative Diseases (DZNE) Göttingen Germany.; Department of Psychiatry and Psychotherapy University Medical Center Göttingen University of Göttingen Göttingen Germany.; Department of Medical Sciences Neurosciences and Signaling Group Institute of Biomedicine (iBiMED) University of Aveiro Aveiro Portugal., Hansen N; Department of Psychiatry and Psychotherapy University Medical Center Göttingen University of Göttingen Göttingen Germany., Rostamzadeh A; Department of Psychiatry Medical Faculty University of Cologne Cologne Germany., Düzel E; German Center for Neurodegenerative Diseases (DZNE) Magdeburg Germany.; Institute of Cognitive Neurology and Dementia Research (IKND) Otto-von-Guericke University Magdeburg Germany., Glanz W; German Center for Neurodegenerative Diseases (DZNE) Magdeburg Germany., Incesoy EI; German Center for Neurodegenerative Diseases (DZNE) Magdeburg Germany.; Institute of Cognitive Neurology and Dementia Research (IKND) Otto-von-Guericke University Magdeburg Germany.; Department for Psychiatry and Psychotherapy University Clinic Magdeburg Magdeburg Germany., Butryn M; German Center for Neurodegenerative Diseases (DZNE) Magdeburg Germany., Buerger K; German Center for Neurodegenerative Diseases (DZNE, Munich) Munich Germany.; Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich Munich Germany., Janowitz D; Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich Munich Germany., Ewers M; German Center for Neurodegenerative Diseases (DZNE, Munich) Munich Germany.; Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich Munich Germany., Perneczky R; German Center for Neurodegenerative Diseases (DZNE, Munich) 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 Rostock Germany., Kilimann I; German Center for Neurodegenerative Diseases (DZNE) Rostock Germany.; Department of Psychosomatic Medicine Rostock University Medical Center Rostock Germany., Goerss D; German Center for Neurodegenerative Diseases (DZNE) Rostock Germany.; Department of Psychosomatic Medicine Rostock University Medical Center 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., Munk MH; German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany.; Department of Psychiatry and Psychotherapy University of Tübingen Tübingen Germany., Sanzenbacher C; German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany., Spottke A; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Department of Neurology University of Bonn Bonn Germany., Roy-Kluth N; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany., Heneka MT; Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg Belvaux Luxemburg., Brosseron F; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany., Wagner M; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany., Wolfsgruber S; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany., Kleineidam L; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany., Stark M; Department of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry University of Bonn Medical Center Bonn Germany., Schmid M; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Institute for Medical Biometry University Hospital Bonn Bonn Germany., Jessen F; German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.; Department of Psychiatry Medical Faculty University of Cologne Cologne Germany.; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) University of Cologne Köln Germany., Bannach O; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany.; attyloid GmbH Düsseldorf Germany., Willbold D; Institute of Biological Information Processing (Structural Biochemistry: IBI-7) Forschungszentrum Jülich GmbH Jülich Germany.; attyloid GmbH Düsseldorf Germany.; Institut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf Düsseldorf Germany., Peters O; Department of Psychiatry and Psychotherapy Charité Berlin Germany.; German Center for Neurodegenerative Diseases (DZNE) Berlin Germany.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (Amsterdam, Netherlands) [Alzheimers Dement (Amst)] 2024 Apr 25; Vol. 16 (2), pp. e12589. Date of Electronic Publication: 2024 Apr 25 (Print Publication: 2024).
DOI: 10.1002/dad2.12589
Abstrakt: Introduction: Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear.
Methods: A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology.
Results: Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T- compared to A-T- and A+T+. APOE   ε 4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected.
Discussion: The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease-modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages.
Highlights: Using surface-based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE-Longitudinal Cognitive Impairment and Dementia (DELCODE) cohortAβ oligomers were significantly elevated in mild cognitive impairment (MCI)Amyloid-positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid-negative control groupInterestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanisms.
Competing Interests: Dieter Willbold and Oliver Bannach are co‐founders and shareholders of attyloid GmbH. This had no influence of the interpretation of the data. All other authors declare no competing interests related to this work. The sFIDA method is protected by patents EP3271724A1, EP3014279B1 and EP2794655B1. Author disclosures are available in the supporting information.
(© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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