Tau conformation, distribution and PET imaging correlations in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings.