P-tau235: a novel biomarker for staging preclinical Alzheimer's disease

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...

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Detalles Bibliográficos
Autores: Lantero Rodriguez, Juan, Snellman, Anniina, Benedet, Andrea L., Milà Alomà, Marta, Camporesi, Elena, Montoliu-Gaya, Laia, Ashton, Nicholas J., Vrillon, Agathe, Karikari, Thomas K., Gispert, Juan Domingo, Salvadó, Gemma, Shekari, Mahnaz, Toomey, Christina E., Lashley, Tammaryn L., Zetterberg, Henrik, Suárez-Calvet, Marc, Brinkmalm, Gunnar, Rosa-Neto, Pedro, Blennow, Kaj
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/53340
Acceso en línea:http://hdl.handle.net/10230/53340
http://dx.doi.org/10.15252/emmm.202115098
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
CSF
Biomarkers
P-tau235
Tau
Descripción
Sumario: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.

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