Sjors Scheres, Research Leader, Structural Studies Division, MRC Laboratory of Molecular Biology, Cambridge, UK, will give a talk on "Cryo-EM structures of amyloids from human brain."

Abstract:  The assembly of microtubule-associated protein tau into abundant amyloid inclusions underlies many neurodegenerative diseases called tauopathies. Tau inclusions display distinct neuroanatomical and cellular distributions between different tauopathies. Morphological and biochemical differences suggest that amyloid filaments of the tau protein adopt disease-specific molecular conformations. Molecular conformers of filamentous tau may give rise to different neuropathological phenotypes, similar to prion strains, but the underlying structures were not known. Using electron cryo-microscopy (cryo-EM), we determined the structures of tau filaments that were extracted from the brains of individuals with many different tauopathies, including Alzheimer’s disease, chronic traumatic encephalopathy (CTE) and progressive supranuclear palsy (PSP). I will give an introduction to the basics of cryo-EM structure determination and explain how our structures have revealed unexpected differences between the tau filaments from the different diseases, and how these structures provide exciting avenues to unravel the mechanisms of amyloid formation in neurodegeneration.