Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Aβ pathology are detected
Marc Suárez-Calvet, Thomas K Karikari, Nicholas J Ashton, Juan Lantero Rodríguez, Marta Milà-Alomà, Juan Domingo Gispert, Gemma Salvadó, Carolina Minguillon, Karine Fauria, Mahnaz Shekari, Oriol Grau-Rivera, Eider M Arenaza-Urquijo, Aleix Sala-Vila, Gonzalo Sánchez-Benavides, José Maria González-de-Echávarri, Gwendlyn Kollmorgen, Erik Stoops, Eugeen Vanmechelen, Henrik Zetterberg, Kaj Blennow, José Luis Molinuevo, ALFA Study, Annabella Beteta, Raffaele Cacciaglia, Alba Cañas, Carme Deulofeu, Irene Cumplido, Ruth Dominguez, Maria Emilio, Carles Falcon, Sherezade Fuentes, Laura Hernandez, Gema Huesa, Jordi Huguet, Paula Marne, Tania Menchón, Grégory Operto, Albina Polo, Sandra Pradas, Anna Soteras, Marc Vilanova, Natalia Vilor-Tejedor, Marc Suárez-Calvet, Thomas K Karikari, Nicholas J Ashton, Juan Lantero Rodríguez, Marta Milà-Alomà, Juan Domingo Gispert, Gemma Salvadó, Carolina Minguillon, Karine Fauria, Mahnaz Shekari, Oriol Grau-Rivera, Eider M Arenaza-Urquijo, Aleix Sala-Vila, Gonzalo Sánchez-Benavides, José Maria González-de-Echávarri, Gwendlyn Kollmorgen, Erik Stoops, Eugeen Vanmechelen, Henrik Zetterberg, Kaj Blennow, José Luis Molinuevo, ALFA Study, Annabella Beteta, Raffaele Cacciaglia, Alba Cañas, Carme Deulofeu, Irene Cumplido, Ruth Dominguez, Maria Emilio, Carles Falcon, Sherezade Fuentes, Laura Hernandez, Gema Huesa, Jordi Huguet, Paula Marne, Tania Menchón, Grégory Operto, Albina Polo, Sandra Pradas, Anna Soteras, Marc Vilanova, Natalia Vilor-Tejedor
Abstract
In Alzheimer's disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p-tau) in the preclinical stage of the Alzheimer's continuum. We measured three novel CSF p-tau biomarkers, phosphorylated at threonine-181 and threonine-217 with an N-terminal partner antibody and at threonine-231 with a mid-region partner antibody. These were compared with an automated mid-region p-tau181 assay (Elecsys) as the gold standard p-tau measure. We demonstrate that these novel p-tau biomarkers increase more prominently in preclinical Alzheimer, when only subtle changes of amyloid-β (Aβ) pathology are detected, and can accurately differentiate Aβ-positive from Aβ-negative cognitively unimpaired individuals. Moreover, we show that the novel plasma N-terminal p-tau181 biomarker is mildly but significantly increased in the preclinical stage. Our results support the idea that early changes in neuronal tau metabolism in preclinical Alzheimer, likely in response to Aβ exposure, can be detected with these novel p-tau assays.
Keywords: Alzheimer’s disease; biomarker; cerebrospinal fluid; plasma; tau.
Conflict of interest statement
JDG has given lectures in symposia sponsored by the following for‐profit companies: General Electric, Philips and Biogen. GK is a full‐time employee of Roche Diagnostics GmbH. ES is an employee and EVM is a co‐founder of ADx NeuroSciences. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. KB has served as a consultant or at advisory boards for Abcam, Axon, Biogen, Lilly, MagQu, Novartis and Roche Diagnostics, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures‐based platform company at the University of Gothenburg. JLM has served/serves as a consultant or at advisory boards for the following for‐profit companies, or has given lectures in symposia sponsored by the following for‐profit companies: Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, ProMIS Neurosciences. The remaining authors declare that they have no conflict of interest.
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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Source: PubMed