Tau seeding activity in Alzheimer's disease: Characteristics, factors, and applications.

Abstract

The prion-like seeding activity (SA) of misfolded microtubule-associated protein tau (MAPT, tau) drives neuropathological progression in Alzheimer's disease (AD), offering a dynamic biomarker beyond static quantitative measures. Recent advances in biomarker research have highlighted the importance of tau seeding activity (TSA), a prion-like propagation mechanism, in the early diagnosis and monitoring of AD. TSA reflects the dynamic process of pathological tau aggregation and spread across brain regions, offering a potential tool for predicting disease progression and differentiating AD from other tauopathies. This article reviews the structural and functional characteristics of tau, the mechanisms underlying its SA, and the impact of post-translational modifications on tau propagation. We also discuss the limitations of current diagnostic methods, which rely on static quantitative measures of tau levels, and propose that tau SA could serve as a more comprehensive biomarker for early diagnosis and risk assessment in asymptomatic individuals. Furthermore, we explore the translational potential of TSA in precision medicine, emphasizing the need for standardized detection methods and clinical validation. By integrating TSA with neuroimaging and fluid biomarkers, a multi-dimensional predictive framework could be established to guide individualized therapeutic strategies and improve diagnostic accuracy in AD and related tauopathies.