Saliva Alpha-synuclein Levels in LRRK2 Mutation Carriers

Study Rationale:
Biomarkers (markers of disease activity) are needed to help determine a diagnosis of Parkinson's disease (PD) and to monitor disease progression. Reduced cerebrospinal fluid (baths the brain and spinal cord; CSF) levels of the alpha-synuclein protein is the most consistent potential PD biomarker to date; however, obtaining CSF samples is not always practical. Therefore, the Zhang lab investigated the biomarker potential of alpha-synuclein in a more readily accessible body fluid, saliva, and found that it tended to be lower in those with PD compared to those without PD and possibly reduced as the severity of motor symptoms increased. In the current study, we aim to further investigate the biomarker potential of salivary alpha-synuclein in a unique group of participants with possible pre-clinical PD who carry LRRK2 mutations.

Hypothesis:
We wish to determine if saliva alpha-synuclein levels are decreased in those who currently do not have clinical symptoms of PD but may develop PD in the future and whether saliva alpha-synuclein levels decrease further once clinical symptoms appear and the disease progresses.

Study Design:
We will measure and compare alpha-synuclein levels in the saliva of LRRK2 mutation carriers that do not have PD symptoms (possibly pre-clinical PD), LRRK2 mutation carriers that show symptoms (clinical PD), as well as those without LRRK2 mutations by using one or more assays (tests).

Impact on Diagnosis/Treatment of Parkinson's Disease:
Human salivary alpha-synuclein could be a reliable, inexpensive, easily accessible (with essentially no side effects associated with collection) biomarker that can assist with early PD diagnosis when clinical diagnosis is the most difficult and treatment could be most effective, predict/follow PD progression and evaluate the effectiveness of existing and future treatments.

Next Steps for Development:
Successful results will need to be replicated in a longitudinal study from those with samples collected at multiple time points, including before the appearance of PD symptoms, at clinical diagnosis and over the course of the disease for several years. Ideally, this group should consist of those with non-familial (non-inherited) PD, as 90% of PD cases are not associated with genetic causes (such as LRRK2 mutations).