Prospect of Alpha-Synuclein (A-Syn) Isolation From Saliva as a Promising Diagnostic Biomarker Alternative in Parkinson's Disease (PD): A Systematic Review

Abstract

Neurodegenerative diseases, in particular Parkinson's disease (PD), a disabling disorder, require early attention due to the course the diseases take. By the time of clinical manifestation, dopaminergic neuron death would have already exceeded a damaging level. Therefore, the discovery of biomarkers that will effectively diagnose PD at an early stage and help monitor disease advancement is crucial. Out of the available biomarkers and bodily sources from which these can be isolated; alpha-synuclein (a-syn) from saliva seems to be a promising and easily accessible option. This has been further investigated in this systematic review. A comprehensive literature search on PubMed, PubMed Central (PMC), and Science Direct resulted in 1,439 articles. After screening and exclusion, 12 relevant articles were derived. In many of the studies, there was a decrease in total salivary a-syn in PD patients compared to healthy controls (HC), with an increase in oligo a-syn and oligo a-syn/total a-syn ratio as a rather consistent finding amongst the studies reviewed. On the other hand, a few studies revealed no significant difference in a-syn levels between the controls and PD patients. Another common finding was the lack of disease severity correlation with the marker, probably due to the scarcity of longitudinal studies conducted and smaller cohorts recruited in the studies. Overall, the total a-syn did show a genetic and phenotypic association, whilst oligo a-syn had the potential to serve as a biomarker for disease diagnosis. With the standardization of sample collection methods and diagnostic tools, and the accomplishment of longitudinal studies, further importance of salivary a-syn as a biomarker in PD could be established, utilizing the already existing data as an encouraging foundation for future research.

Keywords: alpha-synuclein oligomer; neurodegenerative disorder; parkinson' s disease; saliva; salivary alpha-synuclein.

Figure 1. PRISMA 2020 flow diagram for systematic reviews, which included searches of databases only

PRISMA: Preferred items for systematic reviews and meta-analysis Criteria sourced from Page et al [9].