Building Disease-associated Tau Amyloids in vitro: Cryo-EM Insights of Polyanion-induced Tau Fibrils
Emily Hernandez
Department of Chemistry & Biochemistry
Faculty Supervisor: Eric Greene
The protein Tau, canonically stabilizes microtubules but also is associated with amyloid inclusions in various neurodegenerative diseases like Alzheimer’s disease among others that are collectively known as tauopathies. Interestingly, each tauopathy disease displays a unique conformational subset of amyloid Tau suggesting a structure-function relationship between Tau amyloid conformation and disease progression/outcome. However, to date no in vitro method has successfully reconstituted all disease-related conformations using full-length 4N0R Tau. Recent evidence has determined that chemical inducers of Tau amyloid formation can produce chemically diverse fibrils that we predict are similar to disease amyloid conformations, but the exact conformations of induced fibrils remain unknown. Cryo-electron microscopy (Cryo-EM) is the only structural method suited for studying Tau amyloid conformations. Thus far, we have preliminary results demonstrating that sodium alginate-induced P301S tau fibrils form straight fibrils with a shallow helical twist. Future work seeks to develop a dictionary of in vitro fibrils associated with each tauopathy conformation of Tau.