The protein tau canonically stabilizes microtubules and is also 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 0N4R tau. Recent evidence has determined that chemical inducers of tau amyloid formation can produce chemically diverse fibrils that are predicted to be 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, preliminary results demonstrate 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.
Hernandez et al. (Sun,) studied this question.