Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease

BACKGROUNDAll individuals with Down syndrome (DS) will develop full-blown Alzheimer<acute accent>s disease (AD) pathology by age 40. Several genes encoded in chromosome 21, including dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), have been proven to contribute to the p...

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Detalles Bibliográficos
Autores: Kac, PR, Alcolea, D, Montoliu-Gaya, L, Fernández, S, Rodriguez, JL, Maure, L, González-Ortiz, F, Benejam, B, Turton, M, Barroeta, I, Harrison, P, Videla, L, Ashton, NJ, Lleó, A, Zetterberg, H, Carmona-Iragui, M, Karikari, TK, Fortea, J, Blennow, K
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p19514
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19514
Access Level:acceso abierto
Palabra clave:Alzheimer<acute accent>s disease
CSF biomarkers
DABNI
Down syndrome
<italic>DYRK1A</italic>
plasma biomarkers
p-tau212
Simoa
SPIN
Descripción
Sumario:BACKGROUNDAll individuals with Down syndrome (DS) will develop full-blown Alzheimer<acute accent>s disease (AD) pathology by age 40. Several genes encoded in chromosome 21, including dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), have been proven to contribute to the pathology. Phosphorylation of tau at threonine-212 (p-tau212) is very sensitive to DYRK1A phosphorylation and is increased in DSAD brain lysates. Here, we assessed the potential of this biomarker in DSAD and sporadic AD.METHODSUsing single molecule array (Simoa) technology, we tested p-tau212 and p-tau181 (n = 245 for plasma, n = 114 matching cerebrospinal fluid [CSF] samples).RESULTSWe have confirmed that the levels of plasma p-tau212 are increased in the DS population and sporadic AD cases, including prodromal and mild cognitive impairment states. Plasma p-tau212 started increasing approximately when people became amyloid positron emission tomography positive.DISCUSSIONPlasma p-tau212 might have utility for theragnostics, monitoring therapy efficacy, and as a target engagement biomarker in clinical trials both in sporadic and DSAD.Highlights Plasma p-tau212 is increased in the Down syndrome (DS) population. Plasma p-tau212 increases approximate to 15 years before the disease onset in DSAD. Plasma p-tau212 accurately differentiates between control and disease groups. Plasma p-tau212 accurately differentiates amyloid beta (A beta)+ and A beta- participants.