Woo MS, Therriault J, Jonaitis EM, Wilson R, Langhough RE, Rahmouni N, Benedet AL, Ashton NJ, Tissot C, Lantero-Rodriguez J, Macedo AC, Servaes S, Wang YT, Arias JF, Hosseini SA, Betthauser TJ, Lussier FZ, Hopewell R, Triana-Baltzer G, Kolb HC, Jeromin A, Kobayashi E, Massarweh G, Friese MA, Klostranec J, Vilali P, Pascoal TA, Gauthier S, Zetterberg H, Blennow K, Johnson SC, Rosa-Neto P.

„Background: 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.
Methods: 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. Findings: 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]). Interpretation: 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.“



EBioMedicine. 2024 Nov:109:105413



Link to Pubmed