Plasma p-tau217 assays effectively predict amyloid status but lack precision for tau staging in Alzheimer's disease

Blood-based biomarkers for Alzheimer's disease (AD) have demonstrated high performance in identifying amyloid-β (Aβ) pathology. However, the diagnostic accuracy of commercial plasma biomarker assays in predicting PET-defined AD stages-particularly late-stage tau accumulation-requires further evaluation. We included 229 participants from the Alzheimer's Disease Neuroimaging Initiative, all of whom underwent amyloid and tau PET imaging and testing with plasma assays. Among the plasma biomarkers, p-tau217 showed the strongest linear and non-linear associations with amyloid and tau PET. When distinguishing A + from A - T - participants, p-tau217 assays achieved the highest accuracy (AUC range: 0.85-0.91), outperforming other plasma biomarkers (AUC range: 0.66-0.81). However, the accuracy of plasma biomarkers, including p-tau217 assays, significantly decreased when differentiating A + T + from A + T - stages (AUC for p-tau217 assays: 0.69-0.77; AUC for other plasma biomarkers: 0.53-0.67; P < 0.05). These findings were replicated in an independent cohort (n = 334). Our study found that among currently available commercial plasma assays, including p-tau217 assays, they demonstrate high accuracy in classifying Aβ status but are less accurate in assessing tau pathology severity in Aβ positive individuals.