Oligomeric α-Syn and SNARE complex proteins in peripheral extracellular vesicles of neural origin are biomarkers for Parkinson's disease

Blood-based biomarkers are needed to be used as easy, reproducible, and non-invasive tools for the diagnosis and prognosis of chronic neurodegenerative disorders including Parkinson's Disease (PD). In PD, aggregated toxic forms of alpha-Synuclein (alpha-Syn) accumulate within neurons in the brain and cause neurodegeneration; alpha-Syn interaction with SNARE proteins also results in synaptic disfunction. We isolated neural derived extravesicles (NDEs) from peripheral blood of 32 PD patients and 40 healthy controls (HC) and measured the concentrations of oligomeric alpha-Syn and of the presinaptic SNARE complex proteins: STX-1A, VAMP-2 and SNAP-25. Oligomeric alpha-Syn was significantly augmented whereas STX-1A and VAMP-2 were significantly reduced in NDEs of PD patients compared to HC (p < 0.001 in all cases). ROC curve analyses confirmed the discriminatory ability of NDEs oligomeric alpha-Syn, STX-1A and VAMP-2 levels to distinguish between PD patients and HC. Oligomeric alpha-Syn NDEs concentration also positively correlated with disease duration and severity of PD. These results are promising and confirm that NDEs cargoes likely reflect core pathogenic intracellular processes in their originating brain cells and could serve as novel easily accessible bio-markers. Further studies are needed to confirm results and eventually for testing rehabilitation programs and drug treatments effects.

Automated summary

Blood-based biomarkers such as oligomeric alpha-Syn and presynaptic SNARE complex proteins show promising potential in diagnosing and predicting Parkinson's Disease. The concentrations of these biomarkers in neural derived extravesicles (NDEs) from peripheral blood correlate with disease duration and severity, indicating their potential as easily accessible and effective tools for monitoring disease progression.