Dr. Anthony Fitzpatrick is the PI of Project 3 (competitive supplement). Dr. Fitzpatrick is an Assistant Professor in the Department of Biochemistry and Molecular Biophysics at Columbia University. The Fitzpatrick lab aims to relate the atomic structure of tau fibril polymorphs directly to biophysical properties responsible for their propagation in vivo using a range of biophysical techniques. He recently determined the atomic structures of tau fibril polymorphs purified directly from AD brain (published in Nature), and his previous studies revealed that amyloid fibril polymorphs have diverse surface properties, thermodynamic stabilities, and material properties. While high-resolution structure determination of amyloid fibrils was previously not possible using cryo-EM, Dr. Fitzpatrick has successfully incorporated advanced image-processing algorithms with state-of-the-art cryo-EM imaging techniques to successfully solve the structure of AD tau filaments. Using this expertise, Dr. Fitzpatrick will now examine the role of genetic factors, such as mutations in the tau gene (MAPT), in determining filament morphology and influencing phenotypic variation in neurodegenerative tauopathies.