Mutations (changes) in protein LRRK2 is the main genetic cause of Parkinson's disease (PD). In the past, we found that LRRK2 interacts with ribosomes, cellular protein factories. We then investigated whether LRRK2 changes the way ribosomes work in cellular and pre-clinical models of Parkinson's. We found that ribosomes made 40 percent less protein in Parkinson's models and in skin cells from people with PD. This finding suggests that reduced protein production may provide a useful biomarker, an objective measure of Parkinson's. By identifying which proteins are out of balance in PD, we may learn more about the disease mechanism.
In this study, we will examine protein production in human blood cells and determine whether we can identify biomarkers that help diagnose PD and track its progression.
We will collect blood samples from people with Parkinson's and from healthy people. We will also collect blood from people with one of the diseases similar to Parkinson's and from people with Alzheimer's disease and use these samples for comparison. From these blood samples, we will extract cells called peripheral blood mononuclear cells and use a research tool called mass spectrometry to discover nascent proteins in these cells. Finally, we will use statistics and mathematical modeling to determine which proteins are better than DaTscan -- a diagnostic method for PD -- at distinguishing between healthy people and people with Parkinson's.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Finding biomarkers that are good at diagnosing and tracking Parkinson's would reduce the time to diagnosis, speed the search for a cure and assist with personalized treatment planning. The proteins identified may also give us and other researchers useful insight into disease mechanism.