Study Rationale: People with Parkinson’s disease (PD) share some common problems, such as stiffness, slowness of movement and tremors. However, these symptoms vary in severity, and individuals often have other nonmotor symptoms — including dementia, depression and constipation — making the disease very variable across individuals. Although we do not know how this variability arises, genetic studies suggest that a range of cellular processes may be involved in driving the onset and progression of PD, and that these processes may vary in importance across individuals.
Hypothesis: We hypothesize that people with clinically different PD experiences and outcomes have significant differences in their blood RNA profiles and that these differences will be apparent in the early stages of the disease.
Study Design: We will use data from the Parkinson’s Progression Marker Initiative to study blood RNA profiles generated from individuals with PD over time. Using RNA-sequencing data, we will capture information about gene expression, splicing and mitochondrial RNA expression and processing. We will then integrate this data with clinical information to determine whether there are transcriptomic signatures that distinguish between patient groups and whether these differences can be identified early in the disease process. Finally, we will use publicly available and separately funded brain transcriptomic data to identify common transcriptomic signatures between brain and blood, particularly in PD patients with dementia.
Impact on Diagnosis/Treatment of Parkinson’s disease: No treatments that slow the underlying progression of PD currently exist. The ability to identify transcriptomic signatures that distinguish between people who have differing severity of PD at diagnosis could improve clinical trial design and target the right treatment to the right patients.
Next Steps for Development: This study will help identify potential blood biomarkers for PD diagnosis and disease progression. Such markers could form the basis for improvements in trial design and personalized care for people with PD.