November 5, 2025

@michaelokun

Are we inching closer to actually seeing alpha-synuclein in living brains? Alpha-synuclein is a protein that clumps in Parkinson's brain cells. In a new paper in Nature Biomedical Engineering, Weiss and colleagues describe a method called Advanced Sensing of Aggregates in Parkinson’s Disease that may enable direct visualization of nanoscale alpha-synuclein assemblies in human brain tissue. Key Points: - This work shows us that we may be edging closer to truly imaging early alpha-synuclein changes in the brain. - Large-scale imaging identified nanoscale assemblies across more than 1.2 million detected alpha-synuclein structures, revealing a potential continuum from tiny aggregates to Lewy bodies. - Disease specific bright nanoscale species appeared in Parkinson’s samples and were clustered near neurons, astrocytes and microglia. - Biochemical and amplification assays confirmed seed-competent assemblies and supported the concept that small aggregates may possibly represent early drivers of pathology. My take: Alpha-synuclein is small and hidden inside cells and thus imaging has been a real challenge. We need better tools, as Ed Boyden taught us www.pdplan.org This paper seems to be a step in the right direction, and there were 5 points that resonated w/ me. 1-Imaging small alpha-synuclein aggregates is moving closer to reality in human brain tissue. 2- Small aggregates are present in healthy brains, however they also shift in Parkinson’s toward brighter and more disease-linked species. 3- A subset of these tiny protein assemblies in Parkinson’s brains appear possibly capable of seeding further aggregation. 4- These assemblies clustered near key cell types suggesting that early involvement of neurons and glial cells may be critical. 5- This work lays important groundwork toward future tools that may one day let us visualize alpha-synuclein biology in living brains. https://www.nature.com/articles/s41551-025-01496-4 #parkinson #mri #radiology #michaelokun #fixelinstitute