Structural Basis for Tau Strain Conformation in CBD and PSP

Principal Investigator: Lukasz Joachimiak, PhD
Center for Alzheimer’s and Neurodegenerative Diseases, UT Southwestern Medical Center

Dallas, TX

In the brain, the tau protein can form an altered shape that clumps together in an ordered manner, and this aggregated form of tau is referred to as an amyloid assembly. These forms of tau in the brain are key features of Alzheimer’s disease (AD), Progressive Supranuclear Palsy (PSP), and Corticobasal Degeneration (CBD). Research has shown that the smallest form of tau that can initiate aggregated assembly formation is a single tau protein, but for it to become capable of converting to an amyloid-forming protein, it has to change from a “good” shape to a “bad” shape. Recent evidence suggests that the “bad” shapes of the tau protein in PSP and CBD patient brains are different from the “bad” tau associated with other diseases. My lab has developed tools that allow the characterization of protein shape isolated from patient brain material. We propose to isolate the tau protein from healthy, PSP, and CBD patient brain tissues, and we will apply our specialized research tools to determine how the “bad” shape of tau isolated from PSP and CBD brains differs from the tau from healthy brains. We anticipate that understanding how the tau protein changes from a normal shape to the different “bad” forms found in disease will provide the blueprint for designing new methods to detect and prevent these devastating diseases in patients.