The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study

阿尔茨海默病协会全球生物标志物标准化联盟 (GBSC) 血浆磷酸化 tau 循环研究

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作者:Nicholas J Ashton, Ashvini Keshavan, Wagner S Brum, Ulf Andreasson, 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 Vandi

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.

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.

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