Suárez-Calvet, M;
Karikari, TK;
Ashton, NJ;
Lantero Rodríguez, J;
Milà-Alomà, M;
Gispert, JD;
Salvadó, G;
... ALFA Study; + view all
(2020)
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.
EMBO Molecular Medicine
, Article e12921. 10.15252/emmm.202012921.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | 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 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/emmm.202012921 |
| Publisher version: | https://doi.org/10.15252/emmm.202012921 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Alzheimer’s disease, biomarker, cerebrospinal fluid, plasma, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10115160 |
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