Medical and Health Sciences, Basic Medicine, Neurosciences, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Neurovetenskaper

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.