P-tau235: a novel biomarker for staging preclinical Alzheimer's disease
| Autor: | Marta Milà-Alomà, Juan Domingo Gispert, T. Lashley, Gunnar Brinkmalm, Elena Camporesi, Nicholas J. Ashton, Pedro Rosa Neto, Andrea Lessa Benedet, Christina E. Toomey, Agathe Vrillon, Juan Lantero-Rodriguez, Gemma Salvadó, Kaj Blennow, Henrik Zetterberg, Marc Suárez-Calvet, Thomas K Karikari, Mahnaz Shekari, Anniina Snellman, Laia Montoliu-Gaya |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Medicine (General) medicine.medical_specialty tau Proteins CSF Disease Brain tissue QH426-470 Article 03 medical and health sciences R5-920 0302 clinical medicine Cerebrospinal fluid Alzheimer Disease P-tau235 Internal medicine Genetics medicine Humans Phosphorylation Pathological 030304 developmental biology 0303 health sciences Amyloid beta-Peptides business.industry Disease progression Articles p‐tau235 3. Good health Clinical trial Targeted mass spectrometry Disease Progression Molecular Medicine Biomarker (medicine) Tau business Alzheimer’s disease 030217 neurology & neurosurgery Biomarkers Neuroscience |
| Zdroj: | EMBO Molecular Medicine EMBO Molecular Medicine, Vol 13, Iss 12, Pp n/a-n/a (2021) |
| Popis: | 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. A combination of mass spectrometry analysis of brain tissue and ultrasensitive immunoassays in three independent CSF cohorts identifies p‐tau235 as a novel biomarker for Alzheimer's disease (AD) – from preclinical stages to dementia. |
| Databáze: | OpenAIRE |
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