Fibril fragmentation generates diversity in seed population

Abstract

Neurodegenerative diseases are characterised by the formation and accumulation of protein fibrils. The mechanism underlaying this aggregation process remains poorly understood. Fibril fragmentation, resulting in seed generation, plays a role in toxicity. Here we provide a quantitative picture of the impact of ultrasound on patient-derived and recombinant fibrils from various diseases. Fragmentation of recombinant Tau fibrils and patient-derived fibrils from Alzheimers Disease, Corticobasal Degeneration and Frontotemporal Dementia generates amyloid and non-amyloid species. Interestingly, patient-derived fibrils are more susceptible to ultrasound than artificial fibrils. Understanding fibril fragmentation and the generation and nature of seeds may provide insights to the molecular mechanism of the disease progression, contributing to the development therapeutic approaches.