Diagnostic performance of plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non-AD dementias : An international multi-center study
Doecke, J.D. (Australian E-Health Research Centre)
Bellomo, G. (University of Perugia)
Vermunt, L. (Amsterdam UMC. University Medical Center)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Halbgebauer, S. (University of Ulm)
in 't Veld, S. (Amsterdam Universitair Medische Centra (Amsterdam, Països Baixos))
Mattsson-Carlgren, N. (Lund University)
Veverova, K. (Charles University)
Fowler, C.J. (The University of Melbourne)
Boonkamp, L. (Vrije Universiteit)
Houtkamp, I.M. (Amsterdam Universitair Medische Centra (Amsterdam, Països Baixos))
Koel-Simmerlink, M. (Vrije Universiteit)
Verberk, I.M.W. (Vrije Universiteit)
Gaetani, L. (University of Perugia)
Toja, A. (University of Perugia)
Wojdała, A.L. (Vrije Universiteit)
Fortea, Juan (Institut de Recerca Sant Pau)
Pijnenburg, Y. (Amsterdam UMC. University Medical Center)
Lemstra, A. (Amsterdam UMC. University Medical Center)
van der Flier, W. (Amsterdam UMC. University Medical Center)
Hort, J. (Charles University)
Hansson, Oskar (Skåne University Hospital (Suècia))
Parnetti, Lucilla (University of Perugia)
Masters, C.L. (The University of Melbourne)
Lleó, Alberto (Institut de Recerca Sant Pau)
González-Escalante, Armand (Institut Hospital del Mar d'Investigacions Mèdiques)
Contador, José (Hospital del Mar (Barcelona, Catalunya))
Suárez-Calvet, Marc (Institut Hospital del Mar d'Investigacions Mèdiques)
Fernández-Lebrero, Aida (Institut Hospital del Mar d'Investigacions Mèdiques)
Puig-Pijoan, Albert (Institut Hospital del Mar d'Investigacions Mèdiques)
Ortiz-Romero, Paula (Institut Hospital del Mar d'Investigacions Mèdiques)
Jiménez-Moyano, Esther (Institut Hospital del Mar d'Investigacions Mèdiques)
Minguillón, Carolina (Institut Hospital del Mar d'Investigacions Mèdiques)
Campo Milán, Marta del (Hospital del Mar (Barcelona, Catalunya))
Teunissen, Charlotte E. (Vrije Universiteit)
Otto, M. (University of Ulm)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2025
Abstract:	INTRODUCTION: Plasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study. METHODS: Plasma samples (n = 1298) were collected from six international centers. Aβ40, Aβ42, GFAP, NfL, and p-tau181 were measured using single molecule array. In each group, AD diagnosis/co-pathology was defined according to cerebrospinal fluid biomarkers or amyloid positron emission tomography. Validations were performed in three separate cohorts via single and dual cut-off models. RESULTS: p-tau181 showed the best area under the curve value to separate AD from frontotemporal dementia, controls, and Aβ- dementia with Lewy bodies. However, this discriminative power could not be reproduced by applying pre-defined cut-offs. DISCUSSION: p-tau181 was the best single plasma marker for detecting AD at any stage. Specific cut-offs are needed to maximize diagnostic performances. Highlights: Phosphorylated tau (p-tau)181 provided a clear differentiation between controls and Alzheimer's disease (AD) participants, with evidence of increased levels in the preclinical stage of AD. Plasma biomarkers demonstrated that when amyloid co-pathology is removed from dementia with Lewy bodies (DLB), only glial fibrillary acidic protein and neurofilament light chain remain to predict DLB. Given the low prevalence of amyloid co-pathology in frontotemporal dementia (FTD), p-tau181 and its ratio with amyloid beta 42 are strong biomarkers to differentiate FTD from AD.
Grants:	Generalitat de Catalunya 2021/SGR-00913 Instituto de Salud Carlos III PI22/00456 Instituto de Salud Carlos III PI19/00155
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; Amyloid beta ; Dementia with Lewy bodies ; Frontotemporal dementia ; Plasma biomarkers
Published in:	Alzheimer's & dementia, Vol. 21 Núm. 6 (june 2025) , p. e14573, ISSN 1552-5279

DOI: 10.1002/alz.14573
PMID: 40551285

17 p, 3.6 MB

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