β-Glucocerebrosidase Activity in GBA-linked Parkinson's Disease: The Type of Mutation Matters.

Objective: To test the relationship between clinically relevant types of GBA mutations (none, risk variants, mild mutations, severe mutations) and β-glucocerebrosidase activity in patients with Parkinson9s disease (PD) in cross-sectional and longitudinal case-control studies. Methods: 481 participants from the Harvard Biomarkers Study (HBS) and the NIH Parkinson Disease Biomarkers Program (PDBP) were analyzed, including 47 PD patients carrying GBA variants (GBA-PD), 247 without a GBA variant (idiopathic PD), and 187 healthy controls. Longitudinal analysis comprised 195 participants with 548 longitudinal measurements over a median follow-up period of 2.0 years (IQR, 1–2 years). Results: β-Glucocerebrosidase activity was low in blood of patients with GBA-PD compared to healthy controls and patients with idiopathic PD, respectively, in HBS (p Conclusions: Residual activity of the β-glucocerebrosidase enzyme measured in blood inversely correlates with clinical severity types of GBA mutations in PD. β-Glucocerebrosidase activity is a quantitative endophenotype that can be non-invasively monitored and therapeutically targeted.