Study Rationale:
Using pre-clinical models of Parkinson' disease (PD), we found CD163-positive macrophages -- immune cells with the CD163 protein on their surface -- to play an active role in neurodegeneration. We also found that in human samples CD163 is modified as a result of PD-related processes in the nervous system. Furthermore, these changes in CD163 correlated with PD symptoms. Together, these findings suggest that CD163 and the cells it is attached to can be used as biomarkers -- objective measures of disease -- that reflect disease-induced changes in the brain and the associated immune response. A detailed investigation will help to fully understand the role of CD163 in Parkinson's and to realize the potential of CD163 as a disease biomarker.
Hypothesis:
We hypothesize that the immune response in Parkinson's disease involves not only microglia, local brain immune cells, but also macrophages, immune cells that can be found throughout the body. This response evolves as PD progresses and actively promotes the disease, creating a disease cycle. We believe that CD163-positive macrophages represent an important sign of the immune response in Parkinson's and reflect evolving changes in the brain that accompany disease progression.
Study Design:
In this project, we aim to validate our earlier findings using samples from patients with Parkinson's disease at different stages. Immune cells in the blood and molecules that signal disease -- biomarkers -- in the blood and cerebrospinal fluid (CSF) will be analyzed. Biomarkers produced by both nerve and immune cells will be measured. We will search the data for correlation between disease signs and the CD163-positive macrophages and will ultimately aim to describe the relationship between the progressive immune response in PD and disease-related changes in the brain.
Impact on Diagnosis/Treatment of Parkinson's disease:
We aim to define CD163 as an easily accessible biomarker useful in diagnosis and tracking of disease progression. In addition, if this study confirms our earlier findings in pre-clinical models suggesting that changes in CD163-positive cells are indeed linked to disease progression, CD163 would emerge as a new therapeutic target.
Next Steps for Development:
In the future, we will use pre-clinical models to better understand the role of CD163 in the function of nerve cells in different brain regions. We will also study CD163 in clinical scenarios where macrophage involvement is particularly relevant, such as PD associated with mutations in the LRKK2 and the GBA genes with the goal of enabling the development of personalized therapeutic strategies.