Scientists Make Discovery For Parkinson Cause

Published in Nature Biomedical Engineering, the findings may help explain how Parkinson’s spreads through the brain and could ultimately guide the development of earlier diagnostic tools and more effective treatments.

Currently, around 166,000 people in the UK live with Parkinson’s disease, a number expected to rise significantly in coming decades. Globally, the total could reach 25 million by 2050. While existing treatments help manage symptoms such as tremors and stiffness, no therapies yet exist that can slow or stop disease progression.

From Lewy Bodies to Oligomers

For over a century, Parkinson’s has been identified by the presence of large protein deposits called Lewy bodies.

Yet many researchers have suspected that the smaller, earlier-forming oligomers might be the true drivers of cell damage.

Measuring just a few nanometers, these oligomers were previously invisible to even the most sensitive equipment.

“Lewy bodies show where the disease has been, not where it is right now,” explained Professor Steven Lee from Cambridge’s Yusuf Hamied Department of Chemistry, who co-led the study. “If we can detect Parkinson’s at its earliest stages, it could reveal how the disease develops and how we might intervene sooner.”

To make this possible, the team developed a method called ASA-PD (Advanced Sensing of Aggregates for Parkinson’s Disease).

Using ultra-sensitive fluorescence microscopy, ASA-PD detects millions of oligomers in post-mortem brain tissue by amplifying their faint signal while suppressing background noise. This level of sensitivity allows researchers to observe and analyze individual oligomers in unprecedented detail.

“This is the first time we’ve been able to look at these protein clusters directly in human brain tissue at this scale,” said co-first author Dr. Rebecca Andrews, who completed the work while at Cambridge. “It opens entirely new doors in Parkinson’s research.”

Detecting the Earliest Signs of Disease

When the team compared brain tissue from individuals with Parkinson’s to healthy samples, they found that both groups contained alpha-synuclein oligomers, but with key differences.

In Parkinson’s patients, the clusters were larger, brighter, and more numerous, suggesting a strong link between their accumulation and disease progression.

The researchers also identified a unique subclass of oligomers that appeared only in Parkinson’s brains. These could represent the earliest visible markers of the disease, possibly forming years before symptoms begin.

“This method doesn’t just give us a snapshot,” said Professor Lucien Weiss of Polytechnique Montréal, a co-lead author. “It provides an atlas of how these protein changes occur across the brain, and similar approaches may help us study Alzheimer’s or Huntington’s in the same way.”

Professor Sonia Gandhi from the Francis Crick Institute added that the ability to detect these clusters in human brain tissue could fundamentally change how scientists approach neurodegenerative disease research. “Breaking through this technological barrier allows us to ask new questions about when and why protein clusters form — and how those changes lead to disease,” she said.

This landmark study represents one of the clearest views yet into Parkinson’s at its earliest stages, offering hope that future therapies might one day target the disease before irreversible damage occurs.