Role of Structural Polymorphisms of Tau Filaments in the Pathological Diversity of Tauopathies

Abstract

Pathological tau protein accumulated in the brain of patients with tauopathies undergoes structural changes into amyloid-like filaments and forms the intracellular deposits that characterize the disease. Structural and biochemical classification of pathogenic tau extracted from patients' brains supports the hypothesis that structural polymorphisms of tau filaments occur in the brain. Additionally, disease-specific tau pathologies are recapitulated in in vitro and in vivo experimental models that mimic tau aggregation and dissemination and indicate that conformation of tau filaments is a key contributor to the pathological diversity in tauopathy. In this review, we describe the structural and biochemical features of pathological tau extracted from the brain of patients with tauopathies and discuss the possible mechanisms underlying amplification and dissemination of pathological tau in the brain.