Brain-derived and in vitro-seeded alpha-synuclein fibrils exhibit distinct biophysical profiles.

The alpha-synuclein (αSyn) seeding amplification assay (SAA) that allows the generation of disease-specific in vitro seeded fibrils (SAA fibrils) is used as a research tool to study the connection between the structure of αSyn fibrils, cellular seeding/spreading, and the clinicopathological manifestations of different synucleinopathies. However, structural differences between human brain-derived and SAA αSyn fibrils have been recently highlighted. Here, we characterize the biophysical properties of the human brain-derived αSyn fibrils from the brains of patients with Parkinson's disease with and without dementia (PD, PDD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and compare them to the 'model' SAA fibrils.