A centiloid-scaled crossover of amyloid and tau influences on plasma p-Tau217 along the Alzheimer’s disease continuum

Plasma p-tau217 reflects both amyloid and tau pathology, but the point at which its dominant association shifts from Aβ to tau remains unclear. We applied a sliding-window approach across three independent cohorts to determine where this transition occurs along the Centiloid continuum. Our analyses consistently identified a distinct inflection point at which plasma p-tau217 begins to track tau more strongly than Aβ. We analyzed data from three cohorts (K-ROAD, ADNI, and TRIAD), combining the ADNI and K-ROAD datasets for analyses because both cohorts used the same ALZpath p-tau217 assay technology and compatible PET quantification pipelines. To characterize how Aβ and tau differentially relate to plasma p-tau217, we performed partial Spearman correlations and a sliding-window analysis to identify the crossover point along the Centiloid continuum. Across all cohorts, plasma p-tau217 showed stronger overall partial correlations with Aβ uptake than with tau uptake. Sliding-window analyses further revealed a consistent crossover at approximately 39 Centiloids, at which the dominant association of plasma p-tau217 shifted from Aβ to tau. Our analyses converged on a transition point near 39 Centiloids, where the predominant pathological correlate of plasma p-tau217 shifted from Aβ to tau. This stage-dependent reversal aligns with the proposed intersection framework and provides empirical support for it.