[en] [en] INTRODUCTION: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline.
METHODS: We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aβ42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia.
RESULTS: We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AβX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline.
DISCUSSION: Our results suggest that assessing the plasma AβX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD.
HIGHLIGHTS: New plasma Aβ42/Aβ40 measurement using immunoprecipitation-immunoassay Plasma Aβ42/Aβ40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivity.
Disciplines :
Neurology
Author, co-author :
Vogelgsang, Jonathan ; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA
Hansen, Niels; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany
Stark, Melina; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany
Wagner, Michael; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany
Klafki, Hans; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany
Morgado, Barbara Marcos; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany
Jahn-Brodmann, Anke; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany
Schott, Björn; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany
Esselmann, Hermann; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany
Kleineidam, Luca; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany
Wolfsgruber, Steffen; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany
Peters, Oliver; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany
Schneider, Luisa-Sophie; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany
Wang, Xiao; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany
Menne, Felix; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Predemtec AG, Rudower Chausee 29, Berlin, Germany
Priller, Josef; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, 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, Eike; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany
Altenstein, Slawek; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany
Lohse, Andrea; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany
Schneider, Anja; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany
Fliessbach, Klaus; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany
Vogt, Ina; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany
Bartels, Claudia; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany
Jessen, Frank; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany ; Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Rostamzadeh, Ayda; Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany
Duezel, Emrah; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Glanz, Wenzel; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Incesoy, Enise; 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, Michaela; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Buerger, Katharina; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany ; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
Janowitz, Daniel; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
Ewers, Michael; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany ; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
Perneczky, Robert; 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, South Kensington, London, UK
Rauchmann, Boris; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany ; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Broomhall, Sheffield, UK ; Department of Neuroradiology, University Hospital LMU, Marchioninistrassee, Munich, Germany
Guersel, Selim; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
Teipel, Stefan; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Kilimann, Ingo; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Goerss, Doreen; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Laske, Christoph; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany
Munk, Matthias; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany ; Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany
Sanzenbacher, Carolin; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany
Spottke, Annika; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurology, University of Bonn, Bonn, Germany
Roy-Kluth, Nina; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Brosseron, Frederic; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany
Ramierez, Alfredo; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases and Geriatric 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 & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, Texas, USA
Schmid, Matthias; German Center for Neurodegenerative Disorders (DZNE), Bonn, Germany ; Institute for Medical Biometry, University Hospital Bonn, Bonn, Germany
Wiltfang, Jens; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany ; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany ; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
This study was funded by the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung, BMBF), project number 13GW0479B.
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