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Insights into Tauopathy Based on the Prion Model

By Dr. Marc Diamond,Director, Center for Alzheimer鈥檚 and Neurodegenrative Diseases, Distinguished Chair in Basic Brain Injury and Repair, Peter O鈥橠onnell Jr. Brain Institute, UTSouthwestern Medical Center, Dallas, Texas, USA.

Meeting ID: 868 0061 3539
Passcode: 535831

Insights into Tauopathy Based on the Prion Model

The prion hypothesis predicts that transcellular propagation of protein assemblies underlies progressive neurodegeneration. A central idea is that unique, self-propagating assembly structures, termed strains, causes distinct tauopathies. Our work in the past decade has provided critical support to this idea. The current state-of-the-art in the structural analysis of strains is cryo-electron microscopy, which reveals a variety of relatively immobile 鈥渃ores鈥� in the fibrils derived from various tauopathies. We have sought to extend the characterization of tau strains using a dynamic analysis based on cell models of tauopathy. We have exploited defined mutagenesis, especially alanine scans, to define amino acids critical for the formation of different tau assemblies. This reveals 鈥渇ingerprints鈥� that define strains based on their propagation from relatively tiny amounts of soluble brain material. Surprisingly, these findings correlate well with structures predicted by cryo-EM, suggesting that cellular models of tauopathy, in addition to being useful to study tau propagation, will also provide structural information about pathogenic tau assemblies. This presentation will inform the audience about the cell biology that underlies tau prion propagation and the characterization of tau strains.