Molecular Medicine Special Seminar: Decoding Structural Polymorphism of Tau Amyloids in Disease

Abstract Tau, a microtubule-associated protein, aggregates into β-sheet-rich amyloids in over 25 neurodegenerative diseases collectively known as tauopathies. Recent breakthroughs in cryo-electron microscopy have uncovered remarkable structural diversity among tau fibrils in different diseases. Yet, a fundamental question remains: how does the intrinsically disordered tau protein adopt distinct amyloid folds across pathological states? In this talk, I will share findings from biochemical, structural, and computational studies that begin to unravel the underlying "folding logic" of tau misfolding. By dissecting these mechanisms, our goal is to inform the design of conformation-specific diagnostics and therapeutics—tools that could transform how we detect and treat tauopathies with molecular precision.