Plasma amyloid beta X‐42/X‐40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease

Vogelgsang, Jonathan ; Hansen, Niels; Stark, Melina; Wagner, Michael; Klafki, Hans; Morgado, Barbara Marcos; Jahn‐Brodmann, Anke; Schott, Björn; Esselmann, Hermann; Bauer, Chris; Schuchhardt, Johannes; Kleineidam, Luca; Wolfsgruber, Steffen; Peters, Oliver; Schneider, Luisa‐Sophie; Wang, Xiao; Menne, Felix; Priller, Josef; Spruth, Eike; Altenstein, Slawek; Lohse, Andrea; Schneider, Anja; Fliessbach, Klaus; Vogt, Ina; Bartels, Claudia; Jessen, Frank; Rostamzadeh, Ayda; Duezel, Emrah; Glanz, Wenzel; Incesoy, Enise; Butryn, Michaela; Buerger, Katharina; Janowitz, Daniel; Ewers, Michael ; Perneczky, Robert ; Rauchmann, Boris S ; Guersel, Selim ; Teipel, Stefan; Kilimann, Ingo; Goerss, Doreen; Laske, Christoph; Munk, Matthias; Sanzenbacher, Carolin; Spottke, Annika; Roy‐Kluth, Nina; Heneka, Michael; Brosseron, Frederic; Ramierez, Alfredo; Schmid, Matthias und Wiltfang, Jens (2024): Plasma amyloid beta X‐42/X‐40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease. In: Alzheimer's & Dementia, Bd. 20, Nr. 8: S. 5132-5142

Abstract

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

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) ; Medizin > Klinikum der LMU München > Klinik und Poliklink für Psychiatrie und Psychotherapie ; Medizin > Klinikum der LMU München > Klinik und Poliklinik für Radiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198