A Head-to-Head Comparison Between Plasma pTau181 and Tau PET Along the Alzheimer?s Disease Continuum

Both plasma tau phosphorylated at threonine-181 (pTau181) and tau PET show potential for detecting Alzheimer's disease (AD) pathology and predicting clinical progression. In this study, we performed a head-to-head comparison between plasma pTau181 and tau PET along the AD continuum. Methods: We included participants from the Amsterdam Dementia Cohort who underwent 18F-flortaucipir (tau) PET and had a plasma sample biobanked within 12 mo from tau PET. Fifty subjective cognitive decline (SCD) participants (31 A3-negative and 19 A3-positive) and 60 A3-positive participants with mild cogni-tive impairment (MCI) or dementia due to AD were included. A subset had 2-y longitudinal plasma pTau181 and tau PET available (n = 40). Longitudinal neuropsychological test data covering 3.2 +/- 2.7 y from both before and after tau PET were available. Plasma pTau181 and tau PET were compared in their accuracies in discriminating between cognitive stage (MCI/AD vs. SCD) and preclinical A3 status (SCD A3 -positive vs. SCD A3-negative), their associations with cross-sectional and longitudinal neuropsychological test performance, and their longi-tudinal changes over time. Results: When discriminating between preclinical A3 status, the area under the curve (AUC) for plasma pTau181 (0.83) and tau PET (entorhinal, 0.87; temporal, 0.85; neocorti-cal, 0.67) were equally high (all DeLong P > 0.05), but tau PET outper-formed plasma pTau181 in discriminating MCI/AD from SCD (AUC for plasma pTau181: 0.74; AUCs for tau PET: entorhinal, 0.89; temporal, 0.92; neocortical, 0.89) (all P < 0.01). Overall, tau PET showed stron-ger associations with cognitive decline and was associated with a wider variety of cognitive tests than plasma pTau181 (plasma pTau181,-0.02 > 3 <-0.12; tau PET,-0.01 > 3 <-0.22). Both plasma pTau181 and tau PET increased more steeply over time in MCI/AD than in SCD (P < 0.05), but only tau PET annual changes were associated with cognitive decline. Conclusion: Our results sug-gest that plasma pTau181 and tau PET perform equally well in identi-fying A3 pathology but that tau PET better monitors disease stage and clinical progression.