Plasma pTau-217 and N-terminal tau (NTA) enhance sensitivity to identify tau PET positivity in amyloid-β positive individuals.

Introduction: We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aβ) positive participants using plasma biomarkers.
Methods: In this cross-sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [ ¹⁸ F]AZD4694 and tau-PET with [ ¹⁸ F]MK6240 and measured plasma levels of total tau, pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers to predict tau positivity in Aβ+ individuals.
Results: Highest associations with tau positivity in Aβ+ individuals were found for plasma pTau-217 (AUC [CI _95% ] = 0.89 [0.82, 0.96]) and NTA-tau (AUC [CI _95% ] = 0.88 [0.91, 0.95]). Combining pTau-217 and NTA-tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI _95%  = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity.
Discussion: The potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice.
Highlights: We found that in a cohort without pre-selection pTau-181, pTau-217, and NTA-tau showed the highest association with tau PET positivity. We found that in Aβ+ individuals pTau-217 and NTA-tau showed the highest association with tau PET positivity. Combining pTau-217 and NTA-tau resulted in the strongest agreement with the tau PET-based classification.
(© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)