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

BACKGROUND: All individuals with Down syndrome (DS) will develop full-blown Alzheimer'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. Ph...

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Detalles Bibliográficos
Autores: Kac, Przemysław R.|||0000-0001-5083-0924, Alcolea, Daniel|||0000-0002-3819-3245, Montoliu-Gaya, L., Fernández, S., Lantero Rodríguez, Juan|||0000-0002-7426-678X, Maure Blesa, Lucia|||0000-0001-5643-7971, González-Ortiz, F., Benejam, Bessy|||0000-0002-6789-8615, Turton, M., Barroeta, Isabel|||0000-0003-2764-7923, Harrison, P., Videla Toro, Laura|||0000-0002-9748-8465, Ashton, Nicholas J.|||0000-0002-3579-8804, Lleó, Alberto|||0000-0002-2568-5478, Zetterberg, Henrik|||0000-0003-3930-4354, Carmona Iragui, Maria|||0000-0001-6914-2339, Karikari, Thomas K.|||0000-0003-1422-4358, Fortea, Juan|||0000-0002-1340-638X, Blennow, Kaj|||0000-0002-1890-4193
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:322600
Acceso en línea:https://ddd.uab.cat/record/322600
https://dx.doi.org/urn:doi:10.1002/alz.70172
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
CSF biomarkers
DABNI
DYRK1A
Down syndrome
SPIN
Simoa
Plasma biomarkers
P-tau212
Descripción
Sumario:BACKGROUND: All individuals with Down syndrome (DS) will develop full-blown Alzheimer'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. METHODS: Using single molecule array (Simoa) technology, we tested p-tau212 and p-tau181 (n = 245 for plasma, n = 114 matching cerebrospinal fluid [CSF] samples). RESULTS: We 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. DISCUSSION: Plasma 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 ≈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 (Aβ)+ and Aβ- participants.

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