Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice
Verberk, I.M.W. (Vrije Universiteit Amsterdam)
Jutte, J. (Vrije Universiteit Amsterdam)
Kingma, M.Y. (Vrije Universiteit Amsterdam)
Vigneswaran, S. (Amsterdam Universitair Medische Centra (Amsterdam, Països Baixos). Amsterdam Neuroscience)
Gouda, M.M.T.E.E. (Vrije Universiteit Amsterdam)
van Engelen, M.P. (Amsterdam Universitair Medische Centra (Amsterdam, Països Baixos). Amsterdam Neuroscience)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Arranz Martínez, Javier (Institut de Recerca Sant Pau)
Fortea, Juan (Institut de Recerca Sant Pau)
Lleó, Alberto (Institut de Recerca Sant Pau)
Chevalier, C. (University Hospitals of Geneva and University of Geneva)
Marizzoni, M. (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
van de Giessen, E.M. (Vrije Universiteit Amsterdam)
Lemstra, A.W. (Vrije Universiteit Amsterdam)
Pijnenburg, Y.A.L. (Vrije Universiteit Amsterdam)
van der Flier, W.M. (Vrije Universiteit Amsterdam)
den Braber, A. (Vrije Universiteit Amsterdam)
Wilson, D. (Quanterix corporation)
Schut, M.C. (Vrije Universiteit Amsterdam)
van Harten, A.C. (Vrije Universiteit Amsterdam)
Teunissen, C.E. (Vrije Universiteit Amsterdam)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	INTRODUCTION: We developed a multimarker blood test result interpretation tool for the clinical dementia practice, including phosphorylated (P-)tau181, amyloid-beta (Abeta)42/40, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). METHODS: We measured the plasma biomarkers with Simoa (n = 1199), applied LASSO regression for biomarker selection and receiver operating characteristics (ROC) analyses to determine diagnostic accuracy. We validated our findings in two independent cohorts and constructed a visualization approach. RESULTS: P-tau181, GFAP, and NfL were selected. This combination had area under the curve (AUC) = 83% to identify amyloid positivity in pre-dementia stages, AUC = 87%-89% to differentiate Alzheimer's or controls from frontotemporal dementia, AUC = 74%-76% to differentiate Alzheimer's or controls from dementia with Lewy bodies. Highly reproducible AUCs were obtained in independent cohorts. The resulting visualization tool includes UpSet plots to visualize the stand-alone biomarker results and density plots to visualize the biomarker results combined. DISCUSSION: Our multimarker blood test interpretation tool is ready for testing in real-world clinical dementia settings. Highlights: We developed a multimarker blood test interpretation tool for clinical dementia practice. Our interpretation tool includes plasma biomarkers P-tau, GFAP, and NfL. Our tool is particularly useful for Alzheimer's and frontotemporal dementia diagnosis.
Grants:	Instituto de Salud Carlos III PI21/00791 Ministerio de Economía y Competitividad PI14/01126 Instituto de Salud Carlos III PI17/01019 Ministerio de Economía y Competitividad PI13/01532 Instituto de Salud Carlos III PI20/01473 Ministerio de Economía y Competitividad PI16/01825 Instituto de Salud Carlos III PI18/00335 Instituto de Salud Carlos III PI19/00882 Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI22/00611 Instituto de Salud Carlos III AC19/00103 Instituto de Salud Carlos III PI17/01896 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-547
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
Published in:	Alzheimer's & dementia, Vol. 20 Núm. 9 (september 2024) , p. 6115-6132, ISSN 1552-5279

DOI: 10.1002/alz.14088
PMID: 39096164

18 p, 1.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles