Objective/Rationale:
Biomarkers are needed for assisting with the diagnosis of Parkinson’s disease (PD) and for monitoring its progression. To date, the most consistent observations pertain to decreased levels of α-synuclein and DJ-1 in the cerebrospinal fluid (CSF) of PD patients. However, obtaining CSF samples is not practical in most cases; therefore, in this proposal, we wish to investigate the roles of salivary α-synuclein and DJ-1, the markers identified in our recent investigations, as potential PD biomarkers.
Project Description:
This project is centered on the optimization of assays for α-synuclein and DJ-1 in saliva, a body fluid that is quite different from human CSF. The other major goal is to investigate major variables, e.g. age, gender, and circadian rhythm, associated with α-synuclein and DJ-1 levels. To optimize the assays, we will test various conditions (e.g. detergent, amount of antibodies, and incubation time) that could potentially affect the levels of α-synuclein and DJ-1 in the saliva. To address the issues of age, gender and circadian rhythm on salivary α-synuclein and DJ-1 levels, we will use the optimized assays to determine the salivary levels of α-synuclein and DJ-1 in 200 saliva samples from a control cohort (subjects are in their 20s-80s with an equal gender distribution). Additionally, we will follow 20 subjects, ages 65-80, with saliva samples collected 4 times/day (every 6 hours) for one week, allowing us to evaluate the circadian rhythm and daily variation of both protein markers.
Relevance to Diagnosis/Treatment of Parkinson’s Disease: Human salivary α-synuclein and DJ-1 could be reliable and inexpensive biomarkers in readily accessible body fluid (with essentially no side effects associated with sample collection) that can 1) assist with PD diagnosis, particularly at the early stage of the disease when the clinical diagnosis is most difficult and the overall treatment could be most effective, 2) predict/follow PD progression, and 3) evaluate the effectiveness of existing and future neuroprotective treatments.
Anticipated Outcome:
It is anticipated that in about one year, sensitive and specific assays for α-synuclein and DJ-1 in human saliva will be developed and readily used in our projects. It is also our goal to make the assays available to other investigators or critical projects like the cohorts enrolled in the PPMI program.
Final Outcome
The best biomarkers tested for Parkinson’s disease thus far are all based on cerebrospinal fluid (CSF) that is in direct contact with the brain and spinal cord. However, obtaining CSF clinically is relatively invasive and not suitable to some subjects, especially when used in screening assays. Recently, we have identified a few key proteins, including alpha-synuclein, in saliva, a body fluid that is readily accessible clinically. This proposal is designed to further develop the assays for Parkinson’s diagnosis, ideally at early stages of the disease, using saliva, as well as to evaluate a few variables such as age and gender. At this point, assays for two proteins, alpha-synuclein and DJ-1 (another important protein involved in Parkinson’s disease), have been optimized and we have demonstrated that age and gender have minimal effects on these two proteins in saliva.