Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue

The defining feature of Parkinson disease (PD) and Lewy body dementia
(LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies
and Lewy neurites. We developed and validated a novel method to amplify
Asyn fibrils extracted from LBD postmortem tissue samples and used solid
state nuclear magnetic resonance (SSNMR) studies to determine atomic
resolution structure. Amplified LBD Asyn fibrils comprise a mixture of
single protofilament and two protofilament fibrils with very low twist.
The protofilament fold is highly similar to the fold determined by a
recent cryo-electron microscopy study for a minority population of twisted
single protofilament fibrils extracted from LBD tissue. These results
expand the structural characterization of LBD Asyn fibrils and enable new
approaches for studies of disease mechanisms, imaging agents and
therapeutics targeting Asyn.