Blood Biomarker Distinguishes Parkinson's from MSA
by Judy George, Contributing Writer, MedPage Today
ATLANTA -- A blood test for exosomal alpha-synuclein distinguished Parkinson's disease from multiple system atrophy (MSA), two closely related synucleinopathies, with high accuracy in a pilot study, researchers reported here at the annual American Neurological Association meeting.
Blood samples showed that fractions of alpha-synuclein in neuronal and oligodendroglial exosomes were different enough to distinguish Parkinson's from MSA patients with 90% sensitivity and specificity, according to Gal Bitan, PhD, and Suman Dutta, PhD, both of the University of California Los Angeles, and colleagues.
"Biomarkers with such high diagnostic power usually require an invasive lumbar puncture or costly brain imaging," Bitan told MedPage Today. "Our methodology, which achieves high diagnostic accuracy using a blood test, can become widely accessible to neurologists everywhere without requiring patients to visit major medical centers."
Both Parkinson's disease (PD) and MSA are characterized by an abnormal deposition of alpha-synuclein aggregates in the brain. "It has long been known that the deposits are in different cell types," Bitan said. "In PD, Lewy bodies are deposited in neurons, whereas in MSA, glial cytoplasmic inclusions are found in oligodendrocytes."
While both Parkinson's and MSA are synucleinopathies, the diseases follow very different courses, noted Claire Henchcliffe, MD, DPhil, of Weill Cornell Medicine in New York, who was not involved with the study.
"Over time, MSA is much more aggressive and the prognosis is really different," Henchcliffe told MedPage Today. "But there is a lot of overlap in their clinical symptomatology and patients are at risk of being misdiagnosed."
In this study, the researchers measured total alpha-synuclein levels -- not just the abnormally aggregated form of the protein -- in exosomes from neurons and oligodendrocytes. They isolated exosomes, nano-sized vesicles shed by cells that carry proteins, lipids, and nucleic acids, from blood samples of 50 healthy controls, 50 Parkinson's disease patients, and 30 MSA patients.
"We expected to find high levels of alpha-synuclein only in neuronal exosomes, not in oligodendrocytic exosomes, from patients with PD and the opposite in exosomes from patients with MSA," Bitan said. "Surprisingly, we found that in both diseases, the levels were much higher than in healthy, age-matched individuals, and that the levels in MSA were significantly higher than those in PD in both cell types."
Only in exosome levels were these differences apparent: "We measured the alpha-synuclein levels directly in the blood and there was no difference at all among the healthy control, PD, and MSA groups, demonstrating that the measurement in the exosomes is crucial for this test to be successful," Bitan said.
The key to distinguishing successfully between Parkinson's and MSA was measuring alpha-synuclein levels in exosomes from both cell types, he pointed out: "The average total levels in each cell type were significantly different between the Parkinson and MSA groups, but there was still quite a lot of overlap between the groups and the separation between them, based on each cell type alone, was moderate. Only when we combined them into one biomarker, the groups separated with high sensitivity and specificity."
This study by Bitan's group is novel in two ways, Henchcliffe observed. First, the researchers found a way to distinguish the source of alpha-synuclein they measured, whether from neurons or oligodendroglia.
Second, they chose to examine alpha-synuclein in exosomes. "We are still in the very early days of figuring out what exosomes do," Henchcliffe said. "It's been thought in the past that they were full of trash and really didn't have a specific function. But more recently, it seems they are really important in cell-to-cell signaling."
If this research points toward something that can be developed into a sensitive diagnostic test, it could help patients avoid months or years of uncertainty, she added. "A really robust diagnostic test like this could help recruitment in clinical trials, too."
The work was supported by the Team Parkinson/Parkinson Alliance, the UCLA American Parkinson's Disease Association Center, and the MSA Coalition. Bitan reported no conflicts of interest.