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 Alzheimer’s 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.