Study Rationale:
There are currently no Parkinson's disease (PD) biomarkers -- objective measures of disease -- in clinical use, but several blood biomarkers are being developed. Some of these biomarkers may be involved in the chain of pathological events leading to PD, while others may simply reflect the disease-associated changes in the immune system. In this study, we will evaluate the ability of monocytes -- immune cells in the blood -- to make new proteins and determine if it can serve as a biomarker for PD. We are especially interested in using this biomarker to determine the stage of disease before first clinical symptoms appear and to link genetic risk factors for PD to changes in immune cells. These changes may also provide additional insight into the mechanism of disease and fuel the discovery of novel biomarkers and therapeutic targets in the immune system.
Hypothesis:
We hypothesize that in Parkinson's disease monocytes will change the way they "read" genes to make proteins -- the process known as gene expression -- including the genes linked to PD, and that these changes in gene expression reflect the stage of PD.
Study Design:
First, we will characterize gene expression in monocytes from 100 individuals with PD and 100 individuals without PD. We will then search for unique changes associated with disease onset or progression and link genetic risk factors for PD to detectable changes in immune cells that may contribute to PD progression. Finally, we will use advanced mathematical approaches to analyze data on genes, proteins and clinical features to identify new genes associated with Parkinson's disease.
Impact on Diagnosis/Treatment of Parkinson's disease:
This study may reveal new blood biomarkers that could aid in early detection and diagnosis of Parkinson's disease. This study could improve our understanding of the role of the immune system in PD and suggest new therapeutic targets for the development of treatments to slow or prevent Parkinson's.
Next Steps for Development:
Further analysis of gene expression will help to establish whether gene expression in monocytes could be used as a diagnostic or progression biomarker. We will also evaluate how well our findings in monocytes translate into microglia, the monocyte-like immune cells permanently residing in the brain.