Investigating PSP and CBD Tau Strain Biology to Support Novel Diagnostic Development

Principal Investigator: Dr. Amanda L. Woerman
University of Massachusetts

Amherst, MA

Tauopathies are a group of neurodegenerative diseases caused by misfolding of the protein tau, which then spreads throughout the brain. Misfolded tau can give rise to a variety of diseases, including PSP and CBD. Increasing evidence indicates that the conformation, or shape, that tau misfolds into determines the clinical presentation and associated neuropathological lesions a patient will develop. Essentially, each disease is caused by a distinct tau strain. An important implication of this hypothesis is that the successful diagnosis and treatment of tauopathy patients may require strain-specific tools. To support translational research efforts, this study will create a working definition for the tau strains responsible for PSP and CBD. The structure of a protein determines several biochemical properties of that protein, including how stable it is under denaturing conditions. As a result, we can use differences in protein stability to biochemically define PSP and CBD tau strains. The structure of protein also dictates its biological activity. We will use cell-based models to measure differences in protein misfolding after exposing cells to tau aggregates isolated from PSP or CBD patient samples. Combining the biochemical and biological definitions of tau strains will enhance our understanding of both PSP and CBD, and will establish a unifying method for differentiating between the two across research laboratories around the world. The cell models created as a result of this work will also support future efforts to develop disease-specific diagnostics and therapeutics.