AD/PD 2022 | Brain region-specific changes in α-synuclein conformations in Parkinson’s disease

Tim Bartels, PhD, University College London, London, UK, describes a study looking at α-synuclein protein conformation ratios in health and disease. The team compared the relative levels of unfolded and helical forms of cytosolic α-synuclein in post-mortem human brain tissue of sporadic Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) cases and healthy brains. They discovered that differences were highly brain region-specific: regions affected by Lewy bodies had a very low tetramer ratio, whilst non-affected regions had high ratios. Overall, there was a difference between disease and control brains, with clear destabilization of the equilibrium of conformations, but also a difference in the brain regions affected in either PD or DLB brains. These findings suggest that neuronal vulnerability in certain brain regions may be mediated by α-synuclein conformation switching. This interview took place at the AD/PD™ 2022 International Conference on Alzheimer’s and Parkinson’s Diseases hosted in Barcelona, Spain.