Study Rationale:
There is growing evidence for a relevant influence of chronic and subtle inflammation on Parkinson’s disease (PD). The most common causes of monogenic (involving one gene) PD are mutations in the gene LRRK2. While the exact function of the product of the gene (the LRRK2 protein) is still unclear, there is evidence of its involvement in immunological pathways, linking LRRK2-PD to the immune system.
Hypothesis:
We hypothesize that LRRK2 mutations initiate the neurodegenerative process. Then, the “activity level” of the immune system influences disease development and progression.
Study Design:
We will measure blood levels of inflammation markers in (i) large cohorts of LRRK2 mutation carriers who do not have overt clinical symptoms of PD, (ii) in LRRK2 mutation carriers who have PD, and (iii) in respective control cohorts (patients with Parkinson’s disease and healthy individuals without LRRK2 mutations).
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The comparison of “activity levels” of the immune system between the above-mentioned cohorts will help us to understand the influence of the immune system on occurrence and progression of symptoms in this monogenic disease. For example, it may enable us to categorize those individuals who may benefit from anti-inflammatory therapies.
Next Steps for Development:
Individuals with a LRRK2 mutation and signs of chronic and subtle inflammation in the blood will be prime candidates for interventional studies with anti-inflammatory medications.