Researchers at Oxford’s Nuffield Department of Clinical Neurosciences have developed a groundbreaking blood-based test to identify the underlying causes of Parkinson’s disease before noticeable symptoms manifest.
This development could revolutionize the early detection of the disease, allowing for the timely introduction of precision therapies currently in clinical trials.
Parkinson’s disease is the second most prevalent neurodegenerative disorder, affecting seven million individuals worldwide, with an expected doubling of cases by 2040.
One of the major challenges in conducting clinical trials for disease modification is identifying patients in the earliest stages of disease development and ruling out other conditions with similar symptoms.
The study revealed that Parkinson’s disease begins more than a decade before clinical symptoms surface, as brain cells struggle to process a small protein called alpha-synuclein.
This leads to the formation of abnormal clumps of alpha-synuclein, damaging vulnerable nerve cells and resulting in the characteristic movement disorders and often dementia.
By the time individuals are diagnosed with Parkinson’s disease, many of these vulnerable nerve cells have already perished, and alpha-synuclein clumps have formed in various brain regions.
The ability to predict whether the pathways responsible for alpha-synuclein are impaired before the onset of symptoms could be a game-changer in identifying individuals who would benefit most from disease-modifying therapies.
In a study published in JAMA Neurology, Shijun Yan and colleagues in the Tofaris lab demonstrated the potential of measuring a subtype of extracellular vesicles to detect changes in alpha-synuclein in individuals at risk of developing Parkinson’s disease.
Extracellular vesicles are tiny particles released by all cell types and present in bodily fluids, including blood, serving as messengers between cells.
The test involves isolating extracellular vesicles originating from nerve cells in the blood and measuring their alpha-synuclein content.
Professor George Tofaris explains the importance of a robust assay, as neuronally-derived extracellular vesicles constitute a small fraction of all circulating vesicles, and most alpha-synuclein in the blood is released by peripheral cells, primarily red blood cells.
In a groundbreaking first, the research team studied 365 at-risk individuals from four clinical cohorts, 282 healthy controls, and 71 people with Parkinson’s disease.
Those at the highest risk of developing Parkinson’s (with over 80% probability) exhibited a twofold increase in alpha-synuclein levels in neuronal extracellular vesicles, effectively distinguishing them from low-risk individuals or healthy controls.
Overall, the test successfully identified individuals at high risk of developing Parkinson’s disease with 90% probability.
Furthermore, the blood test could detect evidence of neurodegeneration or pathology in individuals who had not yet developed movement disorders or dementia.
In a subgroup of 40 individuals who later developed Parkinson’s and related dementia, the blood test was positive in over 80% of cases up to seven years before diagnosis.
The research suggests nerve cells may protect themselves by packaging excess alpha-synuclein in extracellular vesicles released into the blood.
This innovative blood test has the potential to revolutionize the early detection of Parkinson’s disease, enabling timely intervention and targeted therapies.
Further research and clinical trials will confirm these findings and advance the fight against this debilitating disease.
If you care about Parkinson’s disease, please read studies about Vitamin E that may help prevent Parkinson’s disease, and Vitamin D could benefit people with Parkinson’s disease.
For more information about brain health, please see recent studies about new way to treat Parkinson’s disease, and results showing COVID-19 may be linked to Parkinson’s disease.
The research findings can be found in JAMA Neurology.
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