Scientists have, for the first time, directly visualised the protein clusters believed to trigger Parkinson’s, potentially paving the way for new treatments for the disease.

These tiny clusters, known as alpha-synuclein oligomers, have long been considered the likely culprits for Parkinson’s disease to start developing in the brain, but have evaded direct detection in human brain tissue, with researchers describing them as “the needle in the haystack”.

But now, scientists from the University of Cambridge, UCL, the Francis Crick Institute and Polytechnique Montréal have developed an imaging technique that allows them to see, count and compare oligomers in human brain tissue.

There around 166,000 people in the UK who live with Parkinson’s disease. By 2050, the number of people with Parkinson’s worldwide is expected to double to 25 million.

For more than a century, doctors have recognised Parkinson’s by the presence of large protein deposits, known as Lewy bodies.

But some scientists have suspected that smaller, earlier-forming oligomers may cause damage to brain cells. Until now, these oligomers were too small to see – just a few nanometres long.

“Lewy bodies are the hallmark of Parkinson’s, but they essentially tell you where the disease has been, not where it is right now,” said Professor Steven Lee from Cambridge’s Yusuf Hamied Department of Chemistry, who co-led the research.

Lee and his colleagues have developed a technique, called ASA-PD (Advanced Sensing of Aggregates for Parkinson’s Disease), which uses ultra-sensitive fluorescence microscopy to detect and analyse millions of oligomers.

Since oligomers are so small, their signal is weak. ASA-PD maximises the signal while decreasing the background, boosting sensitivity to the point where individual alpha-synuclein oligomers can be observed and studied.

“This is the first time we've been able to look at oligomers directly in human brain tissue at this scale: it’s like being able to see stars in broad daylight,” said co-first author Dr Rebecca Andrews. “It opens new doors in Parkinson’s research.”

For the study, the research team examined post-mortem brain tissue samples from people with Parkinson’s and compared them to healthy individuals of similar age.

They found that oligomers exist in both healthy and Parkinson’s brains, but the main difference was the size of the oligomers, which were larger, brighter and more numerous in disease samples.

Researchers say this discovery suggests a direct link to the progression of Parkinson’s.

“This method doesn’t just give us a snapshot,” said Professor Lucien Weiss from Polytechnique Montréal, who co-led the research. “It offers a whole atlas of protein changes across the brain, and similar technologies could be applied to other neurodegenerative diseases like Alzheimer’s and Huntington’s.”

“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.”