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

Synaptic dysfunction plays a key role in Parkinson 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Ministry of Science and Technology, Taiwan (MOST 110-2314-B-038-096 and NSC 111-2314-B-038-136). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Joint Institutional Review Board of Taipei Medical University (approval no. N201609017 and N201801043). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Please contact the corresponding author (CT Hong). The availability of data and materials requires permission from the TMU-JIRB.