Study Rationale:
It has been observed that immune cells from Parkinson’s disease (PD) blood respond to pathogens in a way that promotes inflammation. However, it is unknown whether this contributes to disease development or changes because of disease onset. Most individuals diagnosed with a sleeping disorder called rapid eye movement (REM) sleep behavior disorder (RBD) are likely to develop PD. By studying immune cells from RBD patients and comparing them to patients already diagnosed with PD and control volunteers, we can begin to determine if changes in immune cells are present in RBD patients and are potentially an early event of PD. In addition, the biological mechanism leading to immune cell dysfunction in PD is not understood, but it has been suggested that lysosome and/or mitochondria may contribute to this.
Hypothesis:
Immune cells from RBD and PD patient blood will, in response to a viral pathogen, have increased responses which promote inflammation compared to those from control volunteers, with PD immune cells being more pro-inflammatory than RBD immune cells. This will be associated with lysosome and/or mitochondria dysfunction.
Study Design:
Two types of white blood cell, monocytes and T cells, will be isolated from the blood of RBD and PD patients and control volunteers. These will then be stimulated with a viral pathogen, influenza, and inflammatory responses will be measured. To try and understand why immune cells may be dysregulated in patient groups, lysosome and mitochondria function will also be measured.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The results from this study will reveal whether changes in immune cell responses to viral pathogens are an early event in Parkinson’s and could therefore be used as a tool to diagnose, monitor progression and predict PD course. The results from this study will also inform us of underlying mechanisms of these immune cell changes associated with lysosomes and/or mitochondria.
Next Steps for Development:
To directly monitor changes in immune cell responses over disease progression, it will be necessary to perform a longitudinal study to monitor changes across time in the same set of RBD patients to monitor and detect potential conversion to PD.