Scientists have, for the first time, directly visualised the protein clusters in the brain believed to trigger Parkinson's disease, bringing them one step closer to potential treatments.
Parkinson's is a progressive incurable neurological disorder that affects the brain, but also the body more widely, and blights the lives of millions.
Patients typically suffer progressive tremors and movement problems that can eventually rob them of the independence.
While scientists have known for years that tiny clusters—called alpha-synuclein oligomers—likely cause Parkinson's to start developing in the brain, until now they have not been able to visualise these proteins in human brain tissue.
But in a breakthrough, experts from the University of Cambridge, University College London, the Francis Crick Institute and Polytechnique Montreal have developed a technique that allows them not only to see these clusters in the brain, but also count them.
For over a century, doctors have confirmed Parkinson's by the presence of large protein deposits, known as Lewy bodies. But now experts say these smaller, earlier-forming clusters may cause the damage to the brain cells associated with Parkinson's.
'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.'
Until now, these oligomers were too small to see at just a few nanometres long, but now the team have developed a technique called Advanced Sensing of Aggregates for Parkinson's Disease (ASA-PD) which uses lasers to mark proteins in post-mortem brain tissue.
Dr Rebecca Andrews, who carried out the lab study, added: 'This is the first time we've been able to look at oligomers directly in human brain tissue at this scale: it's like seeing stars in broad daylight.'
'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 Professor Lucien Weiss, study co-lead author, from Polytechnique Montreal.
In the current study, published in the journal Nature Biomedical Engineering, researchers first analysed post-mortem brain tissue samples from people with Parkinson's and compared them to healthy individuals of a similar age.
Whilst the proteins were detected in both healthy and Parkinson's brains, in Parkinson's patients the oligomers were much larger, brighter and there were more of them—suggesting a direct link to the progression of the disease.
The team also identified a subclass of oligomers that appeared only in Parkinson's patients, which experts say could be the earliest visible markers of the disease—potentially years before classic symptoms appear.
'This method doesn't just give us a snapshot,' explained Prof Weiss.
'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.'
Professor Sonia Gandhi, an expert in neurodegeneration at The Francis Crick Institute, added: 'The only real way to understand what is happening in human disease is to study the human brain directly, but because of the brain's sheer complexity, this is very challenging.'
The researchers now hope that this breakthrough will foster a better understanding of why, where and how these protein clusters form and leads to disease.
Currently diagnosis is normally based on the development of later stage symptoms like terms after other potential health conditions have been ruled out.
Parkinson's charities estimate more than one in four patients with the condition are misdiagnosed before getting the correct diagnosis.
Around 166,000 people in the UK are thought to be living with the debilitating disease, and the number is rising. By 2050, the number of people with Parkinson's worldwide is expected to double to a staggering 25million.
Early signs of Parkinson's include a tremor, stiffness, slowness of movement and loss of smell.
Balance problems such as issues with coordination and muscle cramps are other common signs.
Patients can also, as a consequence of their disease, frequently suffer from mental health problems like depression and anxiety.
While there are drugs that can help alleviate some of the symptoms, caused by the death of nerve cells in the brain that produce dopamine, there are no drugs that can slow to stop the disease itself.
Experts are still working to uncover what triggers the death of these nerves.
However, current thinking is that it's due to a combination of genetic changes and environmental factors.
Risk of developing the condition broadly increases with age, with most patients are diagnosed over 50.
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