Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.
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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, 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, Wiltfang Jens
Аннотация
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.