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

Title: Plasma amyloid beta X‐42/X‐40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease
Authors: Vogelgsang, J.; Hansen, N.; Stark, M.; Wagner, M.; Klafki, H.; Morgado, B.M.; Jahn‐Brodmann, A.; Schott, B.; Esselmann, H.; Bauer, C.; Schuchhardt, J.; Kleineidam, L.; Wolfsgruber, S.; Peters, O.; Schneider, L.; Wang, X.; Menne, F.; Priller, J.; Spruth, E.; Altenstein, S.; Lohse, A.; Schneider, A.; Fliessbach, K.; Vogt, I.; Bartels, C.; Jessen, F.; Rostamzadeh, A.; Duezel, E.; Glanz, W.; Incesoy, E.; Butryn, M.; Buerger, K.; Janowitz, D.; Ewers, M.; Perneczky, R.; Rauchmann, B.; Guersel, S.; Teipel, S.; Kilimann, I.; Goerss, D.; Laske, C.; Munk, M.; Sanzenbacher, C.; Spottke, A.; Roy‐Kluth, N.; Heneka, M.; Brosseron, F.; Ramierez, A.; Schmid, M.; Wiltfang, J.
Publisher Information: Wiley
Publication Year: 2024
Collection: White Rose Research Online (Universities of Leeds, Sheffield & York)
Description: 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
Document Type: article in journal/newspaper
File Description: text
Language: English
ISSN: 1552-5260
Relation: https://eprints.whiterose.ac.uk/id/eprint/214234/1/Alzheimer%20s%20%20%20Dementia%20-%202024%20-%20Vogelgsang%20-%20Plasma%20amyloid%20beta%20X%E2%80%9042%20X%E2%80%9040%20ratio%20and%20cognitive%20decline%20in%20suspected%20early.pdf; Vogelgsang, J. orcid.org/0000-0001-9326-8193 , Hansen, N., Stark, M. et al. (47 more authors) (2024) Plasma amyloid beta X‐42/X‐40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease. Alzheimer's & Dementia, 20 (8). pp. 5132-5142. ISSN: 1552-5260
Availability: https://eprints.whiterose.ac.uk/id/eprint/214234/
Rights: cc_by_nc_nd_4
Accession Number: edsbas.3F301D11
Database: BASE