Research carried out at Oxford’s Nuffield Department of Clinical Neurosciences has led to the development of a new blood-based test to identify the pathology that triggers Parkinson’s disease before the main symptoms occur. This could allow clinicians to screen for those individuals at high risk of developing the disease and facilitate the timely introduction of precision therapies that are currently at clinical trial stage.
Parkinson’s disease starts more than ten years before patients come to the clinic with symptoms because their brain cells fail to handle a small protein called alpha-synuclein. This leads to the formation of abnormal clumps of alpha-synuclein which damage vulnerable nerve cells, causing the familiar movement disorder and often dementia. By the time people are diagnosed with Parkinson’s disease, most of these vulnerable nerve cells have already died and alpha-synuclein clumps have formed in many brain regions.
It would be useful if there was a way to predict whether the pathways that handle alpha-synuclein are impaired before the onset of Parkinson’s symptoms. This could help clinicians to identify people most likely to benefit from disease-modifying therapies when they become available.
In the paper, “Neuronally Derived Extracellular Vesicle α-Synuclein as a Serum Biomarker for Individuals at Risk of Developing Parkinson Disease” in JAMA Neurology, Shijun Yan and colleagues in the Tofaris lab revealed the promise of measuring a subtype of extracellular vesicles to identify changes in alpha-synuclein in people who are likely to develop Parkinson’s disease. Extracellular vesicles are nanoparticles that are released by all cell types and circulate in biofluids including blood, transporting molecular signals between cells.
Using an improved antibody-based assay developed by the research group, the test involves isolating those extracellular vesicles originating from nerve cells from blood, and then measuring their alpha-synuclein content. Professor George Tofaris explains, “A robust assay is crucial because neuronally-derived extracellular vesicles constitute less than 10% of all circulating vesicles, and ~99% of alpha-synuclein in blood is released from peripheral cells, mostly red blood cells.”
In the first study of its kind, the team looked at 365 at-risk individuals from four clinical cohorts (Oxford Discovery, Marburg, Cologne and the US-based Parkinson’s Progression Markers Initiative), 282 healthy controls and 71 people with genetic or sporadic Parkinson’s disease.
They found that those with the highest risk of developing Parkinson’s (more than 80% probability based on research criteria) had a two-fold increase in alpha-synuclein levels in neuronal extracellular vesicles and the test could accurately differentiate them from those with low risk (less than 5% probability) or healthy controls. Overall, the test could distinguish an individual with high risk of developing Parkinson’s from a healthy control with 90% probability.
These findings indicate that the blood test, together with a limited clinical assessment, could be used to screen and identify people who are at high risk of getting the disease. In further analysis, the test could also identify those who had evidence of neurodegeneration detected by imaging, or pathology detected by a spinal fluid assay, but had not yet developed a movement disorder or dementia.
In a small subgroup of 40 people who went on to develop Parkinson’s and related dementia, the blood test was positive in more than 80% of cases up to as much as seven years before the diagnosis.
In this group, there was a trend for higher levels of alpha-synuclein in neuronal extracellular vesicles in the blood to be associated with lower alpha-synuclein in the spinal fluid, and a longer interval before the onset of the main symptoms of Parkinson’s disease. This suggests that the nerve cells may protect themselves by packaging excess alpha-synuclein in extracellular vesicles which are then released in the blood.
The research builds on earlier findings by the Tofaris lab, also confirmed in the current study, showing that the biomarker is increased in patients with Parkinson’s disease but not in other Parkinson’s-like conditions.
The Tofaris lab, which is part of the Nuffield Department of Clinical Neurosciences and based in the Kavli Institute for Nanoscience Discovery, previously delineated the pathway which targets alpha-synuclein for destruction inside nerve cells. This pathway may also direct alpha-synuclein outside cells in extracellular vesicles, when intracellular protein turnover is inefficient in conditions such as aging and Parkinson’s disease.
Professor Tofaris said, “Collectively our studies demonstrate how fundamental investigations in alpha-synuclein biology can be translated into a biomarker for clinical application, in this case for the identification and stratification of Parkinson’s risk. A screening test that could be implemented at scale to identify the disease process early is imperative for the eventual instigation of targeted therapies as is currently done with screening programs for common types of cancer.”
More information: Shijun Yan et al, Neuronally Derived Extracellular Vesicle α-Synuclein as a Serum Biomarker for Individuals at Risk of Developing Parkinson Disease, JAMA Neurology (2023). DOI: 10.1001/jamaneurol.2023.4398
News
Completely New Use Discovered – This Traditional Herb Has Remarkable Nerve Regenerative Properties
Blessed thistle (Cnicus benedictus), a member of the Asteraceae family, thrives in our climate. This plant has been utilized for centuries as a medicinal herb, often consumed as an extract or tea to support [...]
Scientists study lipids cell by cell, making new cancer research possible
Imagine being able to look inside a single cancer cell and see how it communicates with its neighbors. Scientists are celebrating a new technique that lets them study the fatty contents of cancer cells, [...]
Antibiotic Breakthrough: Revolutionary Chinese Study Paves Way for Superbug Defeating Drugs
New research reveals that fluorous lipopetides act as highly effective antibiotics. Bacterial infections resistant to multiple drugs, which no existing antibiotics can treat, represent a significant worldwide challenge. A research group from China has [...]
Signs of Multiple Sclerosis Show Up in Blood Years Before Symptoms Appear
UCSF scientists clear a potential path toward earlier treatment for a disease that affects nearly 1,000,000 people in the United States. By Levi Gadye In a discovery that could hasten treatment for patients with multiple [...]
Advanced RNA Sequencing Reveals the Drivers of New COVID Variants
A study reveals that a new sequencing technique, tARC-seq, can accurately track mutations in SARS-CoV-2, providing insights into the rapid evolution and variant development of the virus. The SARS-CoV-2 virus that causes COVID has the unsettling [...]
No More Endless Boosters? Scientists Develop One-for-All Virus Vaccine
End of the line for endless boosters? Researchers at UC Riverside have developed a new vaccine approach using RNA that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised. Every [...]
How Are Hydrogels Shaping the Future of Biomedicine?
Hydrogels have gained widespread recognition and utilization in biomedical engineering, with their applications dating back to the 1960s when they were first used in contact lens production. Hydrogels are distinguished from other biomaterials in [...]
Nanovials method for immune cell screening uncovers receptors that target prostate cancer
A recent UCLA study demonstrates a new process for screening T cells, part of the body's natural defenses, for characteristics vital to the success of cell-based treatments. The method filters T cells based on [...]
New Research Reveals That Your Sense of Smell May Be Smarter Than You Think
A new study published in the Journal of Neuroscience indicates that the sense of smell is significantly influenced by cues from other senses, whereas the senses of sight and hearing are much less affected. A popular [...]
Deadly bacteria show thirst for human blood: the phenomenon of bacterial vampirism
Some of the world's deadliest bacteria seek out and feed on human blood, a newly-discovered phenomenon researchers are calling "bacterial vampirism." A team led by Washington State University researchers has found the bacteria are [...]
Organ Architects: The Remarkable Cells Shaping Our Development
Finding your way through the winding streets of certain cities can be a real challenge without a map. To orient ourselves, we rely on a variety of information, including digital maps on our phones, [...]
Novel hydrogel removes microplastics from water
Microplastics pose a great threat to human health. These tiny plastic debris can enter our bodies through the water we drink and increase the risk of illnesses. They are also an environmental hazard; found [...]
Researchers Discover New Origin of Deep Brain Waves
Understanding hippocampal activity could improve sleep and cognition therapies. Researchers from the University of California, Irvine’s biomedical engineering department have discovered a new origin for two essential brain waves—slow waves and sleep spindles—that are critical for [...]
The Lifelong Cost of Surviving COVID: Scientists Uncover Long-Term Effects
Many of the individuals released to long-term acute care facilities suffered from conditions that lasted for over a year. Researchers at UC San Francisco studied COVID-19 patients in the United States who survived some of the longest and [...]
Previously Unknown Rogue Immune Key to Chronic Viral Infections Discovered
Scientists discovered a previously unidentified rogue immune cell linked to poor antibody responses in chronic viral infections. Australian researchers have discovered a previously unknown rogue immune cell that can cause poor antibody responses in [...]
Nature’s Betrayal: Unmasking Lead Lurking in Herbal Medicine
A case of lead poisoning due to Ayurvedic medicine use demonstrates the importance of patient history in diagnosis and the need for public health collaboration to prevent similar risks. An article in CMAJ (Canadian Medical Association [...]