Internal Medicine; Epidemiology; Medicine (miscellaneous); Public Health, Environmental and Occupational Health; Assessment and Diagnosis
Abstract :
[en] [en] 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. [en] People with Alzheimer’s disease have difficulties with reasoning and communication. In Alzheimer’s disease, small proteins called amyloid beta (Aβ) stick together, forming tiny clusters in the brain that eventually grow larger. In this study, we aimed to measure these clusters in the blood. When we tested our method on blood samples from 359 people, we surprisingly found that people with Alzheimer’s disease and memory problems had fewer clusters of Aβ compared to healthy individuals. Our finding suggests that genetic factors may influence the body’s ability to clear these clusters from the brain.
Disciplines :
Neurology
Author, co-author :
Blömeke, Lara ; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany ; attyloid GmbH, 40225, Düsseldorf, Germany
Rehn, Fabian ; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany ; attyloid GmbH, 40225, Düsseldorf, Germany
Pils, Marlene ; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany ; attyloid GmbH, 40225, Düsseldorf, Germany
Kraemer-Schulien, Victoria ; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany
Cousin, Anneliese; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany
Kutzsche, Janine ; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany
Bujnicki, Tuyen ; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany
Freiesleben, Silka D ; 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, Luisa-Sophie ; 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, Lukas; 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, Josef; 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, Eike 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
Altenstein, Slawek; 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, Anja ; 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, Klaus; 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, Jens ; 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, Niels ; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, 37075, Goettingen, Germany
Rostamzadeh, Ayda; Department of Psychiatry, University of Cologne, Medical Faculty, 50924, Cologne, Germany
Düzel, Emrah; 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, Wenzel; German Center for Neurodegenerative Diseases (DZNE), 39120, Magdeburg, Germany
Incesoy, Enise I ; 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, Katharina; 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, Daniel; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, 81377, Munich, Germany
Ewers, Michael; 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, Robert; 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, Boris-Stephan; 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, Stefan; German Center for Neurodegenerative Diseases (DZNE), 18147, Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, 18147, Rostock, Germany
Kilimann, Ingo; German Center for Neurodegenerative Diseases (DZNE), 18147, Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, 18147, Rostock, Germany
Laske, Christoph; 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, Matthias H; German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany ; Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany
Spottke, Annika; 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, Nina; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany
Brosseron, Frederic ; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany
Wagner, Michael ; 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, Sandra; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany
Ramirez, Alfredo ; 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, Matthias; German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Bonn, Germany ; Institute for Medical Biometry, University Hospital Bonn, 53127, Bonn, Germany
Jessen, Frank; 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, Oliver; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany ; attyloid GmbH, 40225, Düsseldorf, Germany
Peters, Oliver; 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, Dieter ; 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
We thank Dr. Carsten Korth (Institute of Neuropathology, Universit\u00E4tsklinikum D\u00FCsseldorf, 40225 D\u00FCsseldorf, Germany) who kindly provided the IC16 antibody. We thank Dr. Volker Nischwitz (Central Institute of Engineering, Electronics and Analytics (ZEA-3), Forschungszentrum J\u00FClich, 52428 J\u00FClich, Germany) for ICP-MS measurements of silica nanoparticles. We thank Dr. Andrew Dingley for proof-reding the manuscript. This work was supported by the Helmholtz Association [grant number HVF0079].
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