Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease

Abstract

Mutations in the glucocerebrosidase (GBA1) gene, the most common genetic contributor to Parkinson's disease (PD), are associated with an increased risk of PD in heterozygous and homozygous carriers. While glucocerebrosidase enzyme (GCase) activity is consistently low in Gaucher disease, there is a range of leukocyte GCase activity in healthy heterozygous GBA1 mutation carriers. To determine whether GCase activity may be a marker for PD with heterozygous GBA1 mutations (GBA1 mutation PD, GBA PD), GBA PD patients (n=15) were compared to PD patients without heterozygous GBA1 mutations (idiopathic PD; n=8), heterozygous GBA1 carriers without PD (asymptomatic carriers; n=4), and biallelic mutation carriers with PD (Gaucher disease with PD, GD1 PD; n=3) in a pilot study. GCase activity (nmol/mg protein/hour) in GD1 PD (median [interquartile range]; minimum-maximum: 6.4 [5.7]; 5.3-11) was lower than that of GBA PD (16.0 [7.0]; 11-40) (p=0.01), while GCase activity in GBA PD was lower than idiopathic PD (28.5 [15.0]; 16-56) (p=0.01) and asymptomatic carriers (25.5 [2.5]; 23-27) (p=0.04). Therefore, GCase activity appears to be a possible marker of heterozygous GBA1 mutation PD, and larger studies are warranted. Prospective studies are also necessary to determine whether lower GCase activity precedes development of PD.

Keywords: Biomarker; GBA; GBA enzyme activity; Gaucher; Glucocerebrosidase; Parkinson’s disease.

Fig. 1. Glucocerebrosidase enzyme (GCase) activity

Asymptomatic carriers = GBA1 mutation carriers without Parkinson’s disease, GBA1 mutation PD = monoallelic GBA1 mutation carriers with Parkinson’s disease, GD1 PD = biallelic GBA1 mutation carriers with Parkinson’s disease, idiopathic PD = Parkinson’s disease participants without GBA1 mutations. ** GCase activity in GD1 PD (median 6.4, interquartile range 5.7) was lower than GBA1 mutation PD (p=0.01). Each point represents the GCase activity measured for an individual.