Examining GCase Activity in People with REM Sleep Behavior Disorder

Study Rationale:
Approximately 80 percent of people with REM sleep behavior disorder (RBD) will develop a neurological disorder such as Parkinson's disease (PD). GBA mutations are the most frequent genetic risk factor for PD and occur in 5 to 10 percent of people with PD and 10 to 15 percent of people with RBD. GBA mutations decrease the activity of the protein GCase, which scientists believe plays a role in PD.

Hypothesis:
We will determine if GCase activity is reduced in people with RBD and explore if GCase activity could predict Parkinson's in people with RBD.

Study Design:
About 300 people with RBD and 300 people without RBD who have given blood samples in the past will be recruited in Montreal, Canada, and Oxford, UK, for this project. A clinical neurological examination will be conducted, and the participants will provide new blood samples. Blood samples will be tested for GBA mutations and GCase activity.

Impact on Diagnosis/Treatment of Parkinson's Disease:
It is unclear to what degree GCase activity changes in the early stages of PD. If changes are present early on (in RBD, for example), the GCase pathway could be modulated to prevent progression of prodromal disease.

Next Steps for Development:
If this work finds differences in GCase levels among people with RBD, these findings will be validated in a larger cohort.