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Seeded Propagation Of Tau Fibrils, Paul David Dinkel

Electronic Theses and Dissertations

In various neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, Pick's disease, and corticobasal degeneration, the deposition of fibrils composed of misfolded tau protein is observed. Recent evidence suggests that tau fibrils transfer between cells and spread throughout the brain, underscoring the significance of fibril propagation.

Six tau isoforms exist in the adult human brain that can be grouped into 4-repeat (4R) tau and 3-repeat (3R) tau based on the presence or absence of the second of four microtubule binding repeats. We demonstrate in vitro that seeded fibril growth, a prerequisite for the spreading of the tau pathology, is crucially …