Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Autor:	Blömeke L; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.; attyloid GmbH, 40225, Düsseldorf, Germany., Rehn F; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.; attyloid GmbH, 40225, Düsseldorf, Germany., Pils M; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.; attyloid GmbH, 40225, Düsseldorf, Germany., Kraemer-Schulien V; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany., Cousin A; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany., Kutzsche J; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany., Bujnicki T; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany., Freiesleben SD; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.; Department of Psychiatry and Neuroscience, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany., Schneider LS; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.; Department of Psychiatry and Neuroscience, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany., Preis L; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.; Department of Psychiatry and Neuroscience, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany., Priller J; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.; School of Medicine, Technical University of Munich; Department of Psychiatry and Psychotherapy, 81675, Munich, Germany.; University of Edinburgh and UK DRI, Edinburgh, UK., Spruth EJ; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany., Altenstein S; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany., Schneider A; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany.; University of Bonn Medical Center, Dept. of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, 53127, Bonn, Germany., Fliessbach K; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany.; University of Bonn Medical Center, Dept. of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, 53127, Bonn, Germany., Wiltfang J; German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, 37075, Goettingen, Germany.; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal., Hansen N; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, 37075, Goettingen, Germany., Rostamzadeh A; Department of Psychiatry, University of Cologne, Medical Faculty, 50924, Cologne, Germany., Düzel E; German Center for Neurodegenerative Diseases (DZNE), 39120, Magdeburg, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, 39106, Magdeburg, Germany., Glanz W; German Center for Neurodegenerative Diseases (DZNE), 39120, Magdeburg, Germany., Incesoy EI; German Center for Neurodegenerative Diseases (DZNE), 39120, Magdeburg, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, 39106, Magdeburg, Germany.; Department for Psychiatry and Psychotherapy, University Clinic Magdeburg, 39120, Magdeburg, Germany., Buerger K; German Center for Neurodegenerative Diseases (DZNE, Munich), 81377, Munich, Germany.; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, 81377, Munich, Germany., Janowitz D; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, 81377, Munich, Germany., Ewers M; German Center for Neurodegenerative Diseases (DZNE, Munich), 81377, Munich, Germany.; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, 81377, Munich, Germany., Perneczky R; German Center for Neurodegenerative Diseases (DZNE, Munich), 81377, Munich, Germany.; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, 81377, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy) Munich, 81377, 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, 81377, Munich, Germany.; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.; Department of Neuroradiology, University Hospital LMU, 81377, Munich, Germany., Teipel S; German Center for Neurodegenerative Diseases (DZNE), 18147, Rostock, Germany.; Department of Psychosomatic Medicine, Rostock University Medical Center, 18147, Rostock, Germany., Kilimann I; German Center for Neurodegenerative Diseases (DZNE), 18147, Rostock, Germany.; Department of Psychosomatic Medicine, Rostock University Medical Center, 18147, Rostock, Germany., Laske C; German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany., Munk MH; German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.; Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany., Spottke A; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany.; University of Bonn Medical Center, Dept. of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, 53127, Bonn, Germany.; University of Bonn Medical Center, Dept. of Neurology, 53217, Bonn, Germany., Roy N; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany., Heneka MT; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367, Belvaux, Luxembourg., Brosseron F; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany., Wagner M; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany.; University of Bonn Medical Center, Dept. of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, 53127, Bonn, Germany., Roeske S; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany., Ramirez A; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany.; University of Bonn Medical Center, Dept. of Neurodegenerative Disease and Geriatric Psychiatry/Psychiatry, 53127, Bonn, Germany.; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany.; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.; Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA., Schmid M; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany.; Institute for Medical Biometry, University Hospital Bonn, 53127, Bonn, Germany., Jessen F; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, 37075, Goettingen, Germany.; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany., Bannach O; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.; attyloid GmbH, 40225, Düsseldorf, Germany., Peters O; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.; Department of Psychiatry and Neuroscience, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany., Willbold D; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany. d.willbold@fz-juelich.de.; attyloid GmbH, 40225, Düsseldorf, Germany. d.willbold@fz-juelich.de.; Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany. d.willbold@fz-juelich.de.
Jazyk:	angličtina
Zdroj:	Communications medicine [Commun Med (Lond)] 2024 Dec 10; Vol. 4 (1), pp. 262. Date of Electronic Publication: 2024 Dec 10.
DOI:	10.1038/s43856-024-00690-w
Abstrakt:	Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components. Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma. Results: The blood-based sFIDA assay delivers a sensitivity of 1.8 fM, an inter- and intra-assay variation below 20% for oligomer calibration standards and no interference with matrix components. Quantification of Aβ oligomers in 359 plasma samples from the DELCODE cohort reveals lower oligomer concentrations in subjective cognitive decline and AD patients than healthy Control participants. Conclusions: Correlation analysis between CSF and plasma oligomer concentrations indicates an impaired clearance of Aβ oligomers that is dependent on the ApoE ε4 status. Competing Interests: Competing interests: D.W. and O.B. are co-founders and shareholders of attyloid GmbH. This affiliation had no influence of the interpretation of the data. All other authors declare no competing interests related to this work. (© 2024. The Author(s).)
Databáze:	MEDLINE
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