For the first time, scientists have observed protein clusters believed to trigger Parkinson’s in human brain tissue, paving the way for new diagnostics and treatments.
In a pioneering breakthrough, scientists have directly visualized and quantified the protein clusters believed to initiate Parkinson’s disease, offering hope for new diagnostic and therapeutic approaches to the world’s fastest-growing neurological disorder.
These microscopic protein clusters, known as alpha-synuclein oligomers, have long been suspected of causing Parkinson’s disease but had eluded direct observation in human brain tissue — until now.
Researchers from the University of Cambridge, University College London (UCL), The Francis Crick Institute and Polytechnique Montréal have developed a novel imaging technique that can detect, count and compare these oligomers in post-mortem human brain tissue.
The team’s findings, published in the journal Nature Biomedical Engineering, could unravel the mechanisms of how Parkinson’s disease spreads through the brain and aid in developing diagnostics and treatments.
Advances in this research come at a crucial time, as approximately 166,000 people in the UK live with Parkinson’s, with the global number expected to double to 25 million by 2050.
Parkinson’s disease has traditionally been diagnosed by the presence of large protein deposits called Lewy bodies.
However, scientists have theorized that smaller, earlier-forming oligomers might inflict the damage on brain cells. Until now, these oligomers, just a few nanometers long, have been too tiny to see.
“Lewy bodies are the hallmark of Parkinson’s, but they essentially tell you where the disease has been, not where it is right now,” Steven Lee, a professor of biophysical chemistry in Cambridge’s Yusuf Hamied Department of Chemistry who co-led the research, said in a news release. “If we can observe Parkinson’s at its earliest stages, that would tell us a whole lot more about how the disease develops in the brain and how we might be able to treat it.”
The researchers developed a technique called Advanced Sensing of Aggregates for Parkinson’s Disease (ASA-PD), using ultra-sensitive fluorescence microscopy to detect and study millions of oligomers in brain tissue.
Due to their minuscule size, the technique maximizes the signal while reducing background noise, dramatically boosting sensitivity.
“This is the first time we’ve been able to look at oligomers directly in human brain tissue at this scale,” added co-first author Rebecca Andrews, who conducted the study as a postdoctoral scholar in Lee’s lab. “It’s like being able to see stars in broad daylight. It opens new doors in Parkinson’s research.”
The study compared post-mortem brain tissue samples from individuals with Parkinson’s to those from healthy individuals of similar age.
The results showed oligomers in both groups, but they were more numerous, larger and brighter in Parkinson’s disease samples. This suggests a direct link to the disease’s progression.
Furthermore, a sub-class of oligomers appeared only in Parkinson’s patients, which could serve as early markers of the disease, potentially detectable years before symptoms manifest.
“Oligomers have been the needle in the haystack, but now that we know where those needles are, it could help us target specific cell types in certain regions of the brain,” added Lucien Weiss, an associate professor in the Department of Engineering Physics at Polytechnique Montréal.
Potential applications of this research extend beyond Parkinson’s.
“[S]imilar technologies could be applied to other neurodegenerative diseases like Alzheimer’s and Huntington’s,” Weiss added.
Sonia Gandhi, a senior group leader of the Neurodegeneration Biology Laboratory and an assistant research director at The Francis Crick Institute who co-led the research, emphasized the importance of this breakthrough.
“We hope that breaking through this technological barrier will allow us to understand why, where and how protein clusters form and how this changes the brain environment and leads to disease,” she said in the news release.
Source: University of Cambridge