The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.
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Ashton Nicholas J, Keshavan Ashvini, Brum Wagner S, Andreasson Ulf, Arslan Burak, Droescher Mathias, Barghorn Stefan, Vanbrabant Jeroen, Lambrechts Charlotte, Van Loo Maxime, Stoops Erik, Iyengar Shweta, Ji HaYeun, Xu Xiaomei, Forrest-Hay Alex, Zhang Bingqing, Luo Yuling, Jeromin Andreas, Vandijck Manu, Bastard Nathalie Le, Kolb Hartmuth, Triana-Baltzer Gallen, Bali Divya, Janelidze Shorena, Yang Shieh-Yueh, Demos Catherine, Romero Daniel, Sigal George, Wohlstadter Jacob, Malyavantham Kishore, Khare Meenakshi, Jethwa Alexander, Stoeckl Laura, Gobom Johan, Kac Przemysław R, Gonzalez-Ortiz Fernando, Montoliu-Gaya Laia, Hansson Oskar, Rissman Robert A, Carrillo Maria C, Shaw Leslie M, Blennow Kaj, Schott Jonathan M, Zetterberg Henrik
Аннотация
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.