The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho‐tau Round Robin study
Nicholas J. Ashton, Ashvini Keshavan, Wagner S. Brum, Ulf Andréasson, Burak Arslan, Mathias Droescher, Stefan Barghorn, Jeroen Vanbrabant, Charlotte Lambrechts, Maxime Van Loo, Erik Stoops, Shweta Iyengar, HaYeun Ji, Xiaomei Xu, Alex Forrest‐Hay, Bingqing Zhang, Yuling Luo, Andreas Jeromin, Manu Vandijck, Nathalie Le Bastard, Hartmuth C. Kolb, Gallen Triana‐Baltzer, Divya Bali, Shorena Janelidze, Shieh‐Yueh Yang, Catherine Demos, Daniel Romero, George B. Sigal, Jacob N. Wohlstadter, Kishore S. Malyavantham, Meenakshi Khare, Alexander Jethwa, Laura Stoeckl, Johan Gobom, Przemysław R. Kac, Fernando González‐Ortiz, Laia Montoliu‐Gaya, Oskar Hansson, Robert A. Rissman, María C. Carrillo, Leslie M. Shaw, Kaj Blennow, Jonathan M. Schott, Henrik Zetterberg
Abstract
INTRODUCTION: The Alzheimer's Association Global Biomarker Standardization Consortium conducted a blinded case-control study to learn which phosphorylated tau (p-tau) assays provide the largest fold-changes in Alzheimer's disease (AD) versus non-AD and show commutability in measuring patient samples and candidate certified reference materials (CRMs). METHODS: Thirty-three different p-tau assays measured paired plasma and cerebrospinal fluid (CSF) from 40 participants (25 with "AD pathology" and 15 with "non-AD pathology" by CSF amyloid beta [Aβ]42/Aβ40 and p-tau181 criteria). Four CRMs were assessed. RESULTS: Plasma p-tau217 demonstrated higher fold-changes between AD and non-AD than other p-tau epitopes. Fujirebio LUMIPULSE G, UGOT IPMS, and Lilly MSD p-tau217 provided the highest fold-changes. Plasma p-tau217 showed the strongest correlations between plasma assays (rho = 0.81-0.97). The CRMs were not commutable across assays. DISCUSSION: Plasma p-tau217 showed larger fold-changes and better accuracy for detecting AD pathology in symptomatic individuals, with greater cross-platform agreement than other p-tau variants. Further work is needed to develop suitable CRMs facilitating cross-assay standardization. HIGHLIGHTS: Paired plasma and cerebrospinal fluid (CSF) samples from twenty-five Alzheimer's disease (AD) and 15 non-AD patients were measured blind. Thirty-three plasma assays were compared, for phosphorylated tau-181 (p-tau181), 205, 212, 217 and 231. Plasma p-tau217 consistently had the highest fold-change and was best correlated between assays. Plasma-CSF correlations were weak to moderate. There was lack of commutability for four candidate reference materials.