Combined measure of salivary alpha-synuclein species as diagnostic biomarker for Parkinson’s disease

Parkinson's disease (PD) diagnosis is still vulnerable to bias, and a definitive diagnosis often relies on post-mortem neuropathological diagnosis. In this regard, alpha-synuclein (& alpha;syn)-specific in vivo biomarkers remain a critical unmet need, based on its relevance in the neuropathology. Specifically, content changes in & alpha;syn species such as total (tot-& alpha;syn), oligomeric (o-& alpha;syn), and phosphorylated (p-& alpha;syn) within the cerebrospinal fluid (CSF) and peripheral fluids (i.e., blood and saliva) have been proposed as PD biomarkers possibly reflecting the neuropathological outcome. Here, we measured the p-& alpha;syn levels in the saliva from 15 PD patients along with tot-& alpha;syn, o-& alpha;syn and their ratios, and compared the results with those from 23 healthy subjects (HS), matched per age and sex. We also calculated the optimal cutoff values for different & alpha;syn species to provide information about their capability to discriminate PD from HS. We found that p-& alpha;syn was the most abundant alpha-synuclein species in the saliva. While p-& alpha;syn concentration did not differ between PD and HS when adjusted for total salivary proteins, the ratio p-& alpha;syn/tot-& alpha;syn was largely lower in PD patients than in HS. Moreover, the concentration of o-& alpha;syn was increased in the saliva of PD patients, and tot-& alpha;syn did not differ between PD and HS. The ROC curves indicated that no single & alpha;syn form or ratio could provide an accurate diagnosis of PD. On the other hand, the ratio of different items, namely p-& alpha;syn/tot-& alpha;syn and o-& alpha;syn, yielded more satisfactory diagnostic accuracy, suggesting that the combined measure of different species in the saliva may show more promises as a diagnostic means for PD.