Parkinson’s ‘trigger’ directly observed in post-mortem human brain tissue for the first time

Good news! Better diagnosis, better treatment!

That this study was only done on post-mortem brain tissue is possibly a critical limitation!

"These tiny clusters, called alpha-synuclein oligomers, have long been considered the likely culprits for Parkinson’s disease to start developing in the brain, but until now, they have evaded direct detection in human brain tissue.

Now, researchers ... have developed an imaging technique that allows them to see, count and compare oligomers in human brain tissue ..."

From the abstract:

"Parkinson’s disease (PD) is a neurodegenerative condition characterized by the presence of intraneuronal aggregates containing fibrillar ɑ-synuclein known as Lewy bodies. These large end-stage species are formed by smaller soluble protein nanoscale assemblies, often termed oligomers, which are proposed as early drivers of pathogenesis.

Until now, this hypothesis has remained controversial, at least in part because it has not been possible to directly visualize nanoscale assemblies in human brain tissue. Here we present Advanced Sensing of Aggregates Parkinson’s Disease, an imaging method to generate large-scale α-synuclein aggregate maps in post-mortem human brain tissue. We combined autofluorescence suppression with single-molecule fluorescence microscopy, which together enable the detection of nanoscale α-synuclein aggregates.

To demonstrate the use of this platform, we analysed ~1.2 million nanoscale aggregates from the anterior cingulate cortex in human post-mortem brain samples from patients with PD and healthy controls.

Our data reveal a disease-specific shift in a subpopulation of nanoscale assemblies that represent an early feature of the proteinopathy that underlies PD. We anticipate that quantitative information about this distribution provided by Advanced Sensing of Aggregates—Parkinson’s Disease will enable mechanistic studies to reveal the pathological processes caused by α-synuclein aggregation."

Parkinson’s ‘trigger’ directly observed in human brain tissue for the first time | University of Cambridge "Scientists have, for the first time, directly visualised and quantified the protein clusters believed to trigger Parkinson’s, marking a major advance in the study of the world’s fastest-growing neurological disease."

Large-scale visualization of α-synuclein oligomers in Parkinson’s disease brain tissue (open access)

Fig. 1: ASA–PD.