Study Rationale:
Inherited mutations in the LRRK2 gene are a common cause of Parkinson's disease that presents with clinical symptoms and brain changes similar to idiopathic (cause unknown) Parkinson's. However, it is uncertain if the mechanisms of mutant LRRK2-caused Parkinson's translate to idiopathic Parkinson's disease. This is a key question because small molecules that modulate the activity of the LRRK2 protein -- higher in people with LRRK2 gene mutations -- are a focus of drug development. If there are shared mechanisms of disease, these drugs may serve the broader Parkinson's population.
Hypothesis:
We hypothesize that there are changes in LRRK2 protein activity in brain tissue from people with idiopathic Parkinson's disease.
Study Design:
We will employ two imaging techniques to compare LRRK2 protein activity in various brain regions in post-mortem brain tissue from control volunteers and from people diagnosed and neuropathologically validated as having idiopathic Parkinson's disease.
Impact on Diagnosis/Treatment of Parkinson's Disease:
If we observe and verify enhanced LRRK2 activity in tissue from people with idiopathic Parkinson's disease, we will provide support for the notion that LRRK2-targeting drugs would be useful not only for people with LRRK2 mutations but also for people with Parkinson's of unknown cause. Additionally, measuring enhanced LRRK2 protein activity could be useful for post-mortem classification of Parkinson's disease.
Next Steps for Development:
If we verify enhanced LRRK2 activity in idiopathic Parkinson's brain tissue, these findings could encourage testing of LRRK2-targeting drugs in a broader Parkinson's population.