Biomarker May Distinguish Parkinson's From MSA

Nancy A. Melville

October 22, 2018

ATLANTA — Levels of alpha-synuclein — a key synaptic protein found in brain-derived blood exosomes from patients with Parkinson's disease, dementia, or Lewy body disease — are highly accurate in distinguishing between Parkinson's disease and multiple system atrophy (MSA) and has potential as a sensitive biomarker of these diseases, new research suggests.

"We expect that this new test will offer an earlier diagnosis with a higher degree of certainty for patients with Parkinson's disease and MSA," senior author Gal Bitan, PhD, professor, Department of Neurology, the David Geffen School of Medicine, University of California, Los Angeles (UCLA), told Medscape Medical News.

"Today, the diagnosis relies primarily on the clinical exam, and even the best movement disorders specialists make quite a lot of mistakes," he explained.

Distinguishing Parkinson's disease from MSA, as well as from dementia with Lewy bodies, can be a diagnostic challenge, owing to the many overlapping symptoms of the neurodegenerative disorders. The difficulty can create lengthy delays in arriving at proper diagnoses and treatment.

Studies have shown that alpha-synuclein activity plays an important role in causing neural dysfunction and neurodegeneration in these diseases. Importantly, recent research has revealed that alpha-synuclein is transferred via exosomes — nano-sized vesicles that are shed by cells. The investigators presented their findings here at ANA 2018: 143rd Annual Meeting of the American Neurological Association.

To determine whether levels of alpha-synuclein in serum exosomes could help distinguish between patients with Parkinson's disease, MSA, and healthy persons, Bitan, first author Suman Dutta, PhD, and colleagues at UCLA isolated neuronal and oligodendroglial exosomes from 50 healthy control persons, 50 patients with Parkinson's disease, and 30 patients with MSA.

Using electrochemiluminescence enzyme-linked immunosorbent assay to measure alpha-synuclein, the authors found that concentrations of the protein were significantly higher in the exosomes of patients with Parkinson's and MSA compared to control persons.

In oligodendroglial exosomes, levels of alpha-synuclein distinguished patients with MSA from healthy control persons with as much as 100% sensitivity and 96% specificity.

Importantly, the ratio between the neuronal and oligodendroglial cell types allowed the investigators to distinguish between Parkinson's disease and MSA with 90.0% sensitivity and 90.0% specificity.

The findings are novel — and better than expected, Bitan said.

"The absolute values of alpha-synuclein in neuronal and oligodendroglial exosomes provided moderate separation between the Parkinson's disease and MSA groups," he said.

"Some studies have been able to get similar numbers, though mostly in smaller numbers of patients, using analysis of cerebrospinal fluid, but this is the first time we have been able to do it using a simple blood test," he said.

Although the accuracy of the findings must be validated, if the results are confirmed, the findings could feasibly benefit other patients with other diseases and help with understanding disease progression, Bitan said.

"There is a lot to do — the first step is to validate the results in another cohort. Then we hope to improve the diagnostic accuracy above 90%, and are already working on that," he explained.

"We also would like to expand the scope and apply the methodology to additional neurological diseases. Another direction is to use the biomarker not only for diagnosis but also for measurement of disease progression, which in turn will allow us to assess the effect of new treatments," he said.

The results of the ongoing work will help determine how the blood test can be used in clinical practice, Bitan said.

"There is more development work to be done before it is readily available, and the measurement itself may have to be done in a specialized lab/company, but our hope and goal is to make it available to clinics everywhere," he said.

The authors have disclosed no relevant financial relationships.

ANA 2018: 143rd Annual Meeting of the American Neurological Association. Abstract 632, presented October 22, 2018.

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