Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease
Kac, Przemysław R. (University of Gothenburg)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Montoliu-Gaya, L. (University of Gothenburg)
Fernández, S. (Fundació Catalana Síndrome de Down)
Rodriguez, J.L. (University of Gothenburg)
Maure, L. (Fundació Catalana Síndrome de Down)
González-Ortiz, F. (Sahlgrenska University Hospital)
Benejam, Bessy (Fundació Catalana Síndrome de Down)
Turton, M. (Bioventix Plc)
Barroeta, Isabel (Fundació Catalana Síndrome de Down)
Harrison, P. (Bioventix Plc)
Videla Toro, Laura (Fundació Catalana Síndrome de Down)
Ashton, Nicholas J. (King's College London)
Lleó, Alberto (Institut de Recerca Sant Pau)
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit))
Carmona Iragui, María (Fundació Catalana Síndrome de Down)
Karikari, Thomas K. (University of Pittsburgh)
Fortea, Juan (Fundació Catalana Síndrome de Down)
Blennow, Kaj (University of Science and Technology of China and First Affiliated Hospital of USTC)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2025
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI20/01473 Instituto de Salud Carlos III PI23/01786 Instituto de Salud Carlos III INT21/00073 European Commission R61AG066543 European Commission R01 AG061566 European Commission R21 AG056974 European Commission R01 AG056850 European Commission R01 AG081394
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; CSF biomarkers ; DABNI ; DYRK1A ; Down syndrome ; SPIN ; Simoa ; Plasma biomarkers ; P-tau212
Published in:	Alzheimer's & dementia, Vol. 21 Núm. 4 (april 2025) , p. e70172, ISSN 1552-5279

DOI: 10.1002/alz.70172
PMID: 40275833

13 p, 702.5 KB

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