The search for a reliable, early-disease biomarker for Parkinson’s disease (PD) that reflects underlying pathology is a high priority in PD research. Salivary alpha-synuclein (α-Syn) is an easily accessible biomarker for PD with promising results. Our aim was to evaluate the performance of salivary α-Syn as a diagnostic biomarker of PD. We identified 476 studies through a systematic literature review according to PRISMA guidelines. Finally, eight studies reporting data on salivary α-Syn were included in the review (1240 participants). The quality of studies was assessed by Newcastle–Ottawa scale. (1) Three studies showed that the total α-Syn levels were significantly lower in PD patients compared to healthy controls, while in another five there was no significant association. (2) In some studies, total salivary α-Syn was associated with demographic and clinical features; however, no consistent pattern emerged. In one study, total α-Syn levels were associated with poor cognitive performance in PD patients. (3) Four studies showed a higher salivary oligomeric α-Syn and oligomeric α-Syn/total α-Syn ratio in PD compared to healthy controls, while in another four there was no association. (4) One study concluded that genetic polymorphisms may influence total salivary α-Syn in PD patients. Taken together, the potential of salivary total α-Syn as a PD biomarker is still uncertain, whereas salivary oligomeric α-Syn appears quite promising. Pre-analytical and analytical factors of included studies were important limitations to justify the introduction of salivary α-Syn into clinical practice.
