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
This Startup Says It Can Clean Your Blood of Microplastics
This is a non-exhaustive list of places microplastics have been found: Mount Everest, the Mariana Trench, Antarctic snow, clouds, plankton, turtles, whales, cattle, birds, tap water, beer, salt, human placentas, semen, breast milk, feces, testicles, [...]
New Blood Test Detects Alzheimer’s and Tracks Its Progression With 92% Accuracy
The new test could help identify which patients are most likely to benefit from new Alzheimer’s drugs. A newly developed blood test for Alzheimer’s disease not only helps confirm the presence of the condition but also [...]
The CDC buried a measles forecast that stressed the need for vaccinations
This story was originally published on ProPublica, a nonprofit newsroom that investigates abuses of power. Sign up to receive our biggest stories as soon as they’re published. ProPublica — Leaders at the Centers for Disease Control and Prevention [...]
Light-Driven Plasmonic Microrobots for Nanoparticle Manipulation
A recent study published in Nature Communications presents a new microrobotic platform designed to improve the precision and versatility of nanoparticle manipulation using light. Led by Jin Qin and colleagues, the research addresses limitations in traditional [...]
Cancer’s “Master Switch” Blocked for Good in Landmark Study
Researchers discovered peptides that permanently block a key cancer protein once thought untreatable, using a new screening method to test their effectiveness inside cells. For the first time, scientists have identified promising drug candidates [...]
AI self-cloning claims: A new frontier or a looming threat?
Chinese scientists claim that some AI models can replicate themselves and protect against shutdown. Has artificial intelligence crossed the so-called red line? Chinese researchers have published two reports on arXiv claiming that some artificial [...]
New Drug Turns Human Blood Into Mosquito-Killing Weapon
Nitisinone, a drug for rare diseases, kills mosquitoes when present in human blood and may become a new tool to fight malaria, offering longer-lasting, environmentally safer effects than ivermectin. Controlling mosquito populations is a [...]
DNA Microscopy Creates 3D Maps of Life From the Inside Out
What if you could take a picture of every gene inside a living organism—not with light, but with DNA itself? Scientists at the University of Chicago have pioneered a revolutionary imaging technique called volumetric DNA microscopy. It builds [...]
Scientists Just Captured the Stunning Process That Shapes Chromosomes
Scientists at EMBL have captured how human chromosomes fold into their signature rod shape during cell division, using a groundbreaking method called LoopTrace. By observing overlapping DNA loops forming in high resolution, they revealed that large [...]
Bird Flu Virus Is Mutating Fast – Scientists Say Our Vaccines May Not Be Enough
H5N1 influenza is evolving rapidly, weakening the effectiveness of existing antibodies and increasing its potential threat to humans. Scientists at UNC Charlotte and MIT used high-performance computational modeling to analyze thousands of viral protein-antibody interactions, revealing [...]
Revolutionary Cancer Vaccine Targets All Solid Tumors
The method triggers immune responses that inhibit melanoma, triple-negative breast cancer, lung carcinoma, and ovarian cancer. Cancer treatment vaccines have been in development since 2010, when the first was approved for prostate cancer, followed [...]
Scientists Uncover Hidden Protein Driving Autoimmune Attacks
Scientists have uncovered a critical piece of the puzzle in autoimmune diseases: a protein that helps release immune response molecules. By studying an ultra-rare condition, researchers identified ArfGAP2 as a key player in immune [...]
Mediterranean neutrino observatory sets new limits on quantum gravity
Quantum gravity is the missing link between general relativity and quantum mechanics, the yet-to-be-discovered key to a unified theory capable of explaining both the infinitely large and the infinitely small. The solution to this [...]
Challenging Previous Beliefs: Japanese Scientists Discover Hidden Protector of Heart
A Japanese research team found that the oxidized form of glutathione (GSSG) may protect heart tissue by modifying a key protein, potentially offering a novel therapeutic approach for ischemic heart failure. A new study [...]
Millions May Have Long COVID – So Why Can’t They Get Diagnosed?
Millions of people in England may be living with Long Covid without even realizing it. A large-scale analysis found that nearly 10% suspect they might have the condition but remain uncertain, often due to [...]
Researchers Reveal What Happens to Your Brain When You Don’t Get Enough Sleep
What if poor sleep was doing more than just making you tired? Researchers have discovered that disrupted sleep in older adults interferes with the brain’s ability to clean out waste, leading to memory problems [...]
