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This lecture by the instructor explores the molecular interactions that shape tau polymorphs, focusing on how tau changes conformation to build different assemblies, the structural polymorphisms revealed by cryo-EM structures of tau fibrils, and the impact of tau mutations on disease. The lecture also covers methods to detect tau aggregation, the role of monomeric tau in driving aggregation, and the use of XL-MS to study protein structure. Additionally, it delves into the role of Hsp40s in regulating tau aggregation, the stability differences between 3R and 4R tau fragments, and the engineering of more stable hairpins to control tau aggregation.