Identification of late-stage tau accumulation using plasma phospho-tau217

Abstract

Blood-based disease staging across the Alzheimer's disease (AD) continuum holds the promise to identify individuals that profit from disease-modifying therapies. We set out to identify Braak V+ (Braak V and/or VI) tau PET-positive individuals within amyloid-β (Aβ)-positive individuals using plasma biomarkers. In this cross-sectional study, we assessed 289 individuals from the TRIAD cohort and 306 individuals from the WRAP study across the AD continuum. The participants were evaluated by amyloid-PET with [18F]AZD4694 or [11C]PiB and tau-PET with [18F]MK6240 and measured plasma levels included total tau, phospho-tau isoforms (pTau) pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers using different analytic platforms to predict Braak V+ positivity in Aβ+ individuals. Highest associations with Braak V+ tau positivity in Aβ+ individuals were found for plasma pTau-217+Janssen (AUC [CI95%]=0.97 [0.94, 1.0]) and ALZpath pTau-217 (AUC [CI95%]=0.93 [0.86, 1.0]) in TRIAD. Plasma ALZpath pTau-217 separated Braak V+ tau PET-positive individuals in the WRAP longitudinal study (AUC [CI95%]=0.97 [0.94,1.0]). Thus, we demonstrate that using adjusted cut-offs, plasma pTau-217 identifies individuals with later Braak stage tau accumulation which will be helpful to stratify patients for treatments and clinical studies. This research is supported by the Weston Brain Institute, Canadian Institutes of Health Research (CIHR) [MOP-11-51-31; RFN 152985, 159815, 162303], Canadian Consortium of Neurodegeneration and Aging (CCNA; MOP-11-51-31 -team 1), the Alzheimer's Association [NIRG-12-92090, NIRP-12-259245], Brain Canada Foundation (CFI Project 34874; 33397), the Fonds de Recherche du Québec-Santé (FRQS; Chercheur Boursier, 2020-VICO-279314). P.R-N and SG are members of the CIHR-CCNA Canadian Consortium of Neurodegeneration in Aging. Colin J. Adair Charitable Foundation.