Lantero-Rodriguez, J;
Snellman, A;
Benedet, AL;
Mila-Aloma, M;
Camporesi, E;
Montoliu-Gaya, L;
Ashton, NJ;
... Blennow, K; + view all
(2021)
P-tau235: a novel biomarker for staging preclinical Alzheimer's disease.
EMBO Molecular Medicine
, Article e15098. 10.15252/emmm.202115098.
(In press).
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Abstract
Alzheimer’s disease (AD) is characterised by a long preclinical phase. Although phosphorylated tau (p-tau) species such as p-tau217 and p-tau231 provide accurate detection of early pathological changes, other biomarkers capable of staging disease progression during preclinical AD are still needed. Combining exploratory and targeted mass spectrometry methods in neuropathologically confirmed brain tissue, we observed that p-tau235 is a prominent feature of AD pathology. In addition, p-tau235 seemed to be preceded by p-tau231, in what appeared to be a sequential phosphorylation event. To exploit its biomarker potential in cerebrospinal fluid (CSF), we developed and validated a new p-tau235 Simoa assay. Using three clinical cohorts, we demonstrated that (i) CSF p-235 increases early in AD continuum, and (ii) changes in CSF p-tau235 and p-tau231 levels during preclinical AD are consistent with the sequential phosphorylation evidence in AD brain. In conclusion, CSF p-tau235 appears to be not only a highly specific biomarker of AD but also a promising staging biomarker for the preclinical phase. Thus, it could prove useful tracking disease progression and help enriching clinical trial recruitment.
| Type: | Article |
|---|---|
| Title: | P-tau235: a novel biomarker for staging preclinical Alzheimer's disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/emmm.202115098 |
| Publisher version: | https://doi.org/10.15252/emmm.202115098 |
| Language: | English |
| Additional information: | © 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| 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.ucl.ac.uk/id/eprint/10138660 |
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