Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification

Phosphorylated-tau 217 (pTau217) is currently the most promising blood-based biomarker for accurately detecting Alzheimer's disease (AD) pathology. However, interference from peripheral tau species in the kidneys or peripheral nerves can hinder diagnostic precision. Recently developed brain-derived pTau217 (BD-pTau217) assays emerge as highly specific tools for detecting AD-related pathological changes in the brain. In this study, we conducted a head-to-head comparison of the NULISAqpcr BD-pTau217 assay and Simoa ALZpath total p-Tau217 assay in two independent, amyloid-PET-characterized Chinese cohorts. Our results demonstrate a strong correlation between BD-pTau217 and total pTau217 (ρ = 0.89 to 0.90), with BD-pTau217 showing significantly reduced interference from kidney dysfunction, as evidenced by weaker associations with blood levels of urea (ρ_BD-pTau217 = 0.02 to 0.06, ρ_{Total-pTau217} = 0.06 to 0.12) and creatinine (ρ_BD-pTau217 = 0.03 to 0.08, ρ_{Total-pTau217} = 0.16 to 0.18). Moreover, BD-pTau217 is more strongly associated with amyloid-PET Centiloid values (ρ_BD-pTau217 = 0.78 to 0.80, ρ_{Total-pTau217} = 0.74 to 0.77) and exhibits superior classification performance for amyloid-β (Aβ) pathology (area under the curve [AUC]_BD-pTau217 = 0.96 to 0.98, AUC_{Total-pTau217} = 0.94 to 0.97). Furthermore, BD-pTau217 outperforms total pTau217 for identifying tau-positive individuals within the Aβ-positive group (AUC_BD-pTau217 = 0.89, AUC_{Total-pTau217} = 0.78), facilitating more accurate disease staging. These findings underscore BD-pTau217 as a highly sensitive and specific blood-based biomarker for AD that has significant potential for early detection, precise classification, and staging of AD-related brain pathology in clinical practice.