Test for alpha-synuclein protein may help to diagnose Parkinson’s
Blood test shows high accuracy for detecting protein clumps in study
A test to detect clumping alpha-synuclein protein in the blood — a hallmark of Parkinson’s disease — may help to diagnose the neurodegenerative condition and could also provide insight into how long an individual has been living with Parkinson’s, a new study reports.
The study confirmed that the test had high sensitivity, or accuracy, in detecting such alpha-synuclein protein clumps, or aggregates, in blood samples from Parkinson’s patients.
“In the long term, it is hoped that this blood test can be used to improve the diagnostic security and reliability in PD [Parkinson’s disease], even at early stages during which clinical diagnosis is difficult,” Annika Kluge, MD, and Eva Schaeffer, MD, co-authors of the study at Kiel University in Germany, said in a press release.
“There is currently no blood test for PD available in clinical practice,” the duo added.
Titled “Association of Misfolded α-Synuclein Derived from Neuronal Exosomes in Blood with Parkinson’s Disease Diagnosis and Duration,” the study was published in the Journal of Parkinson’s Disease.
All but one patient in study showed alpha-synuclein protein clumping
Establishing a diagnosis of Parkinson’s disease is based mainly on evaluations of a patient’s symptoms and the results of tests to exclude other disorders. This process is often time-consuming and frustrating for patients and clinicians alike, and a major goal of modern Parkinson’s research is to develop faster, more objective tests to aid in diagnosis.
Although the causes of Parkinson’s are not fully understood, one of the molecular hallmarks of the disease is that the protein alpha-synuclein forms clumps, known as aggregates, in nerve cells. These aggregates are toxic to cells and are thought to contribute to driving the disease.
In previous work, scientists found that exosomes — small packets of cellular material — from nerve cells can be isolated from patients’ blood and tested for clumping alpha-synuclein protein. Here, the scientists tested how well this method can detect Parkinson’s and evaluated the relationship between the results of this blood test and the disease’s duration.
The study included blood samples from 80 Parkinson’s patients with a wide range of disease durations, as well as samples from 20 people who didn’t have Parkinson’s but were similar in terms of age and sex and who served as controls. Slightly more than half of both patients and controls were male, and patients had a mean age of 69 versus 70 for controls.
The results showed that all but one of the Parkinson’s patients were positive for clumping alpha-synuclein on the blood test. By comparison, none of the individuals without Parkinson’s were positive on the test.
The researchers speculated that the one Parkinson’s patient who wasn’t positive for alpha-synuclein clumping might have actually had a different disorder and been misdiagnosed with Parkinson’s, though they emphasized a need for further research to validate this belief.
“It is of course of great importance that the strong results of [this study] are validated and replicated in different labs,” Schaeffer and Kluge said.
Further testing needed to confirm these results
Further analyses showed a statistically significant negative correlation between the extent of alpha-synuclein aggregation seen in the blood test and Parkinson’s duration. In other words, Parkinson’s patients who had been living with the disease for longer tended to have less protein clumping in the blood test.
The researchers stressed that, even though clumping tended to decrease over time, patients who had been living with Parkinson’s for more than 20 years were still positive for clumping, implying that this test does not lose accuracy in late-stage disease.
Given these results, the team said this test “provides an easy to obtain blood-based biomarker, which can identify individuals with [Parkinson’s] with high sensitivity and can be applied even in very late stages of the disease.”
[This test] provides an easy to obtain blood-based biomarker, which can identify individuals with [Parkinson’s] with high sensitivity and can be applied even in very late stages of the disease.
To corroborate these findings, the researchers tested blood samples collected over several years from 11 Parkinson’s patients. Those results showed that the amount of alpha-synuclein clumping consistently decreased over time in 10 of the 11 samples — the one outlier showed an initial decrease in clumping, but then a slight uptick toward the end of follow-up.
These data collectively are consistent with the idea that alpha-synuclein clumping decreases as Parkinson’s progresses. The scientists said it’s not clear why this might be, highlighting an area for future studies to investigate.
“If the decline in seeding activity in blood was confirmed, it may influence further studies and our understanding of disease progression,” Schaeffer and Kluge said.
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