Plasma amyloid beta X‐42/X‐40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease
Jonathan Vogelgsang, Niels Hansen, Melina Stark, Michael Wagner, Hans‐Wolfgang Klafki, Barbara Marcos Morgado, Anke Jahn‐Brodmann, Björn H. Schott, Hermann Esselmann, Chris Bauer, Johannes Schuchhardt, Luca Kleineidam, Steffen Wolfsgruber, Oliver Peters, Luisa‐Sophie Schneider, Xiao Wang, Felix Menne, Josef Priller, Eike Spruth, Slawek Altenstein, Andrea Lohse, Anja Schneider, Klaus Fließbach, Ina R. Vogt, Claudia Bartels, Frank Jessen, Ayda Rostamzadeh, Emrah Duezel, Wenzel Glanz, Enise I. Incesoy, Michaela Butryn, Katharina Büerger, Daniel Janowitz, Michael Ewers, Robert Perneczky, Boris‐Stephan Rauchmann, Selim Guersel, Stefan Teipel, Ingo Kilimann, Doreen Göerß, Christoph Laske, Matthias H. Munk, Carolin Sanzenbacher, Annika Spottke, Nina Roy‐Kluth, Michael T. Heneka, Frederic Brosseron, Alfredo Ramierez, Matthias Schmid, Jens Wiltfang
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.