P-tau235: a novel biomarker for staging preclinical Alzheimer's disease
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- dc.contributor.author Lantero Rodriguez, Juan
- dc.contributor.author Snellman, Anniina
- dc.contributor.author Benedet, Andrea L.
- dc.contributor.author Milà Alomà, Marta
- dc.contributor.author Camporesi, Elena
- dc.contributor.author Montoliu-Gaya, Laia
- dc.contributor.author Ashton, Nicholas J.
- dc.contributor.author Vrillon, Agathe
- dc.contributor.author Karikari, Thomas K.
- dc.contributor.author Domingo Gispert, Juan
- dc.contributor.author Salvadó, Gemma
- dc.contributor.author Shekari, Mahnaz
- dc.contributor.author Toomey, Christina E.
- dc.contributor.author Lashley, Tammaryn L.
- dc.contributor.author Zetterberg, Henrik
- dc.contributor.author Suárez-Calvet, Marc
- dc.contributor.author Brinkmalm, Gunnar
- dc.contributor.author Rosa-Neto, Pedro
- dc.contributor.author Blennow, Kaj
- dc.date.accessioned 2022-06-01T06:26:49Z
- dc.date.available 2022-06-01T06:26:49Z
- dc.date.issued 2021
- dc.description.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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Lantero-Rodriguez J, Snellman A, Benedet AL, Milà-Alomà M, Camporesi E, Montoliu-Gaya L, et al. P-tau235: a novel biomarker for staging preclinical Alzheimer's disease. EMBO Mol Med. 2021 Dec 7; 13(12): e15098. DOI: 10.15252/emmm.202115098
- dc.identifier.doi http://dx.doi.org/10.15252/emmm.202115098
- dc.identifier.issn 1757-4676
- dc.identifier.uri http://hdl.handle.net/10230/53340
- dc.language.iso eng
- dc.publisher Wiley
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/681712
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
- dc.rights Copyright © 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 http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Alzheimer’s disease
- dc.subject.keyword CSF
- dc.subject.keyword Biomarkers
- dc.subject.keyword P-tau235
- dc.subject.keyword Tau
- dc.title P-tau235: a novel biomarker for staging preclinical Alzheimer's disease
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion