New Method May Help Diagnose Parkinson’s Using a Blood Test
A novel method that involves looking for disease-associated alpha-synuclein inside of neuron-derived extracellular vesicles — packets of cellular cargo that are released by nerve cells in the brain, and can be isolated in a person’s blood — may help to diagnose and monitor the progression of Parkinson’s disease.
A team of scientists in Germany described their new approach in the study, “Detection of neuron-derived pathological [alpha]-synuclein in blood,” published in Brain.
“The protocol described here offers the development of a biochemical blood-based test for the diagnosis of Parkinson’s disease,” the scientists wrote.
There is no single test that can diagnose Parkinson’s disease. Currently, the disease is diagnosed based mainly on the presence of symptoms. This means most people with Parkinson’s aren’t diagnosed until the progressive disorder has already caused substantial damage.
“There is an urgent need for an objective and reliable biomarker to improve the diagnostic accuracy of Parkinson’s disease, detect the disease in early stages … and monitor disease progression,” the researchers wrote.
At the cellular level, Parkinson’s is characterized by abnormal aggregates or clumps of the protein alpha-synuclein in brain cells. Some studies have suggested that these disease-associated protein aggregates can be detected in biopsies of tissue or samples of the fluid around the brain. However, collecting these samples is invasive, so the usefulness of the tests in a clinical setting is limited.
Most cells in the body produce extracellular vesicles, or EVs, which are basically small packets of cellular cargo like protein and RNA wrapped in a membrane. EVs are constantly being released and re-absorbed throughout the body, helping to coordinate cell-to-cell communication.
Here, the researchers devised a protocol to isolate EVs from brain nerve cells in the plasma, which is the non-cellular part of blood. Very simply, the protocol involves first using standard centrifugation techniques to isolate all of the EVs in the blood. Then, the EVs specifically released from nerve cells in the brain — termed neuron-derived EVs, or NEs — were identified and filtered out based on the specific protein markers on their surface.
Using this method, the researchers isolated NEs from 30 people with Parkinson’s (ages 46–84) and 50 similarly aged people without the neurological disorder. The team then tested the alpha-synuclein contents of these vesicles.
Results showed that overall alpha-synuclein levels were similar in people with or without Parkinson’s; however, Parkinson’s patients had significantly higher levels of the specific disease-associated version of the protein that forms toxic aggregates. Experiments done in dishes confirmed that alpha-synuclein in Parkinson’s NEs forms the same type of toxic clumps that are associated with the disease.
The researchers noted that the disease-associated form of alpha synuclein “was detected in all Parkinson’s disease patients without any exception and clearly distinguished Parkinson’s disease samples from the control group and vice versa.”
“We conclude that the detection and amplification of pathological [disease-related], soluble [alpha-synuclein] conformers in plasma-NEs is highly promising as a reliable pre-mortem biomarker for Parkinson’s disease,” the team added.
The scientists stressed that more research is needed before this new technique can be translated into a test with clinical applications. The team noted a need to test the method in larger populations, in different stages of Parkinson’s, and also in other diseases characterized by abnormalities in alpha-synuclein, such as Lewy body dementia and multiple system atrophy.
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