Saliva Alpha-synuclein Levels in LRRK2 Mutation Carriers
Research Grant, 2014
Biomarkers are needed to assist with the diagnosis of Parkinsonís disease (PD) and with monitoring its progression. Decreased levels of alpha-synuclein in cerebrospinal fluid is the most consistent biological marker of PD to date; however, obtaining CSF samples is not always practical. Therefore, the Zhang lab investigated alpha-synuclein in a more readily accessible body fluid (saliva) and found that levels tended to be lower in PD patients compared to control subjects and possibly decreased as the severity of motor symptoms increased. In this study we aim to further investigate the biomarker potential of salivary alpha-synuclein in a unique group of subjects with possible pre-clinical PD: LRRK2 mutation carriers.
We wish to determine (i) if saliva alpha-synuclein levels are already decreased in subjects who currently do not have any clinical symptoms but who may go on to develop PD, and (ii) if saliva alpha-synuclein levels decrease further once clinical symptoms appear and the disease progresses.
We will measure and compare alpha-synuclein levels in the saliva of LRRK2 mutation carriers who do not have any PD symptoms (possibly pre-clinical PD subjects), LRRK2 mutation carriers who already do show symptoms (clinical PD subjects), as well as control subjects without LRRK2 mutations utilizing one or more assays.
Impact on Diagnosis/Treatment of Parkinsonís Disease:
Human salivary alpha-synuclein could be a reliable, inexpensive, easily accessible biomarker to 1) assist with early PD diagnosis when treatment could be most effective, 2) predict/follow PD progression, and 3) evaluate the efficacy of existing and future neuroprotective treatments.
Next Steps for Development:
Successful results will need to be replicated in a study with samples collected at multiple time points, including before the appearance of PD symptoms, at clinical diagnosis and over the course of several years of the disease. Ideally, this cohort should consist of patients with non-familial PD as 90 percent of PD cases are not associated with genetic causes (such as LRRK2 mutations).
Director and Endowed Chair of Neuropathology; Professor of Pathology; and Adjunct Professor of Neurology, Ophthalmology and Oral Health Sciences at University of Washington
Location: Seattle, Washington, United States
Assistant Professor of Neurology at University of Toronto
Neurologist at Toronto Western Hospital Movement Disorders Centre
Location: Toronto, Canada
Doctor at BioLegend, Inc.
Location: Boston, Massachusetts, United States