Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson’s disease: A follow-up study

Synaptic dysfunction plays a key role in Parkinson’s disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. This study assessed the efficacy of plasma EV synaptic proteins as biomarkers in PD and their association with disease progression. In total, 144 participants were enrolled, including 101 people with PD (PwP) and 43 healthy controls (HCs). The changes in plasma EV synaptic protein levels between baseline and 1-year follow-up did not differ significantly in both PwP and HCs. In PwP, the changes in plasma EV synaptic protein levels were significantly associated with the changes in unified PD rating scale (UPDRS) part II and III scores. Moreover, PwP with elevated levels (first quartile) of any one plasma EV synaptic proteins (synaptosome-associated protein 25, growth-associated protein 43 or synaptotagmin-1) had significantly greater disease progression in UPDRS part II score and the postural instability and gait disturbance subscore in UPDRS part III than did the other PwP after adjustment for age, sex, and disease duration. These results indicate the promising potential of plasma EV synaptic proteins as clinical biomarkers of disease progression in PD. However, a longer follow-up period is warranted to confirm their role as prognostic biomarkers.