Alpha-synuclein in Blood Serum May Be Early Parkinson’s Biomarker, Study Suggests

Measuring the amount of alpha-synuclein in tiny vesicles collected from blood serum may help diagnose early Parkinson’s and identify patients with different types of this disease.

The study with that finding, “Central Nervous System-Derived Exosomal Alpha-Synuclein in Serum May Be a Biomarker in Parkinson’s Disease,” was published recently in the journal Neuroscience.

As both resting and posture tremor may occur in the early stages of Parkinson’s, patients may be misdiagnosed with essential tremor. Similar to Parkinson’s, essential tremor is a progressive movement disorder, and it predominantly affects hands and arms.

Alpha-synuclein is the main component of Lewy bodies, characteristic protein aggregates that accumulate in brain cells of Parkinson’s patients.

Compared to unaffected individuals, Parkinson’s patients typically have lower levels of alpha-synuclein in their cerebrospinal fluid — the liquid surrounding the brain and spinal cord — which correlates with prognosis. However, measuring alpha-synuclein in the clinic has been precluded by the invasive nature of spinal tap and by the inconsistent results of plasma or serum samples.

Exosomes are tiny vesicles released by neurons and other cells, and have been implicated in the transmission of misfolded proteins, including alpha-synuclein in people with Parkinson’s. As such, researchers hypothesized that exosomes derived from the central nervous system (CNS) could be a peripheral biomarker of Parkinson’s disease.

The scientists recruited 38 newly diagnosed, untreated patients with early Parkinson’s divided into tremor-dominant (TD, 22 patients, mean age 62.7 years) and non-tremor-dominant (NTD, 16 patients, 62.1 years), who were compared to 21 patients with essential tremor (62 years) and 18 healthy controls.

Among the patients with Parkinson’s, those with TD had a shorter disease duration than the people with the NTD subtype (19.2 vs. 35.8 months). The age at disease onset did not differ in these two groups – 61.1 years in TD and 59.1 years in NTS patients.

The results revealed that Parkinson’s patients had lower levels of alpha-synuclein in CNS-derived serum exosomes than those with essential tremor or controls. Importantly, within Parkinson’s patients, those with the NTD type — which has been associated with more frequent depression, lack of motivation and impairment in activities of daily life — had lower amounts than those in the TD subset.

A subsequent analysis found that exosomal alpha-synuclein had a moderate potential to diagnose Parkinson’s disease and a great potential to diagnose non-tremor-dominant patients.

Of note, the amount of CNS-derived alpha-synuclein in exosomes was not significantly associated with disease duration or severity.

Overall, “CNS-derived exosomal [alpha]-synuclein in the serum may be regarded as a biomarker to identify [early Parkinson’s],” the scientists wrote.

Cautioning that studies with larger groups of patients and those with longitudinal monitoring are needed, the team further commented that assessing alpha-synuclein in serum exosomes also may help identify different Parkinson’s types.