Alpha-Synuclein species in oral mucosa as potential biomarkers for multiple system atrophy

The definitive diagnosis of Multiple system atrophy (MSA) requires the evidence of abnormal deposition of α-Synuclein (α-Syn) through brain pathology which is unable to achieve in vivo. Deposition of α-Syn is not limited to the central nervous system (CNS), but also extended to peripheral tissues. Detection of pathological α-Syn deposition in extracerebral tissues also contributes to the diagnosis of MSA. We recently reported the increased expressions of α-Syn, phosphorylated α-Synuclein at Ser129 (pS129), and α-Syn aggregates in oral mucosal cells of Parkinson's disease (PD), which serve as potential biomarkers for PD. To date, little is known about the α-Syn expression pattern in oral mucosa of MSA which is also a synucleinopathy. Here, we intend to investigate whether abnormal α-Syn deposition occurs in oral mucosal cells of MSA, and to determine whether α-Syn, pS129, and α-Syn aggregates in oral mucosa are potential biomarkers for MSA.

The α-Syn levels in oral mucosal cells elevated in patients with MSA, which may be promising biomarkers for MSA.

The oral mucosal cells were collected by using cytobrush from 42 MSA patients (23 MSA-P and 19 MSA-C) and 47 age-matched healthy controls (HCs). Immunofluorescence analysis was used to investigate the presence of α-Syn, pS129, and α-Syn aggregates in the oral mucosal cells. Then, the concentrations of α-Syn species in oral mucosa samples were measured using electrochemiluminescence assays.

Immunofluorescence images indicated elevated α-Syn, pS129, and α-Syn aggregates levels in oral mucosal cells of MSA than HCs. The concentrations of three α-Syn species were significantly higher in oral mucosal cells of MSA than HCs (α-Syn, p < 0.001; pS129, p = 0.042; α-Syn aggregates, p < 0.0001). In MSA patients, the oral mucosa α-Syn levels negatively correlated with disease duration (r = -0.398, p = 0.009). The area under curve (AUC) of receiver operating characteristic (ROC) analysis using an integrative model including age, gender, α-Syn, pS129, and α-Syn aggregates for MSA diagnosis was 0.825, with 73.8% sensitivity and 78.7% specificity.