Study Rationale: Sometimes, a "typo" in a gene called LRRK2 increases the risk of Parkinson's disease (PD), leading to a distinct PD version called LRRK2-PD. While people with LRRK2-PD maintain good thinking skills, they often struggle with balance, likely due to disruptions in a brain chemical called acetylcholine in specific brain regions. By comparing brain scans of LRRK2-PD and typical Parkinson's patients (PD without LRRK-PD “typo”), we aim to uncover unique brain changes, particularly in the acetylcholine pathways, to discover targets for new treatments that specifically target this acetylcholine problem to improving symptoms and slow disease progression in LRRK2-PD.
Hypothesis: We expect to see in the LRRK2-PD, that the brain works harder to use the chemical acetylcholine to make up for and dopamine loss in LRRK2-PD in specific brain regions.
Study Design: We will recruit persons with LRRK2-PD using the pre-existing Parkinson’s Progression Markers Initiative registry, which includes individuals with confirmed diagnoses of the LRRK2-G2019S mutation PD. The recruited participants will undergo clinical assessments, motor testing, MRI scans, and two brain PET scans (dopamine and acetylcholine. We will compare the clinical, motor, and imaging data of these participants with data from PD persons without LRRK2 mutations acquired in our previous studies. This research is expected to be completed within one year.
Impact on Diagnosis/Treatment of Parkinson’s disease: By pinpointing the unique brain changes in LRRK2-PD, we aim to identify targets for treatments that target focus on these specific abnormalities, leading to better care. Figuring out exactly how LRRK2-PD affects the brain in PD will allow development of tailored therapies to improve patient outcomes.
Next Steps for Development: We will be able to identify new, targeted experimental therapeutics for LRRK2-PD informed by a deeper understanding of its disease-causing mechanisms