The Structural Basis of Protein Pathology in Tauopathy
Neurodegenerative diseases such as Alzheimer’s are based on accumulation of the tau protein and have myriad presentations. It is critical to understand the basis of this variability to achieve precise diagnosis and treatment, but current methods of neuropathology are not adequate to explain why patients experience different types of disease. Tau has many characteristics similar to the prion protein, including the formation of distinct, highly ordered assemblies (also termed “strains”) that have unique 3D structures, determining the nature of pathology they cause in the brain. This project combines structural biology, biochemistry, and neuropathology in an attempt to precisely link novel tau structures with specific diseases. It will develop new tools to analyze tau from human brain tissues, with the goal of achieving more precise diagnosis based on quantitative measures. This could enable more personalized approaches to the diagnosis and treatment of neurodegenerative diseases.