Objective: To evaluate glucocerebrosidase (GCase) activity in peripheral blood mononuclear cells (PBMCs) of a cohort of 53 PD patients with and without GBA mutations and controls.

Background: GBA encodes the lysosomal enzyme glucocerebrosidase, important in sphingolipid degradation. Lower glucocerebrosidase enzymatic activity is strongly associated with GBA mutations and modestly with idiopathic Parkinson’s disease. The mechanism by which GBA mutations are linked to Parkinson’s disease remains unknown.

Methods: PBMCs were isolated from fresh blood by standard procedures. Chemiluminescent enzymatic assay was performed using 4MUβG 10 mM as substrate and NaTaurocholate 50 mM incubated at 37°C for 30 min. All patients were genotyped for GBA and LRRK2 mutations.

Results: GBA heterozygotes-PD (n=19) showed a lower GCase activity than patients without GBA mutations (n=34) (mean value 85.5 pmol/min/mg vs 110 pmol/min/mg, p<0.005) and controls (138.47 pmol/min/mg, p=0.0045). A slightly lower enzymatic activity was observed in PD without mutations compared with controls, but that did not reach statistical significance.

Conclusions: GCase activity in PBMCs is significantly reduced in GBA PD. That result suggests that GCase activity may represent a new possible biomarker for GBA-PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/glucocerebrosidase-activity-in-a-cohort-of-pd-patients/