Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease

Roberto A. Ortega, Paola A. Torres, Matthew Swan, William Nichols, Sarah Boschung, Deborah Raymond, Matthew J. Barrett, Brooke A. Johannes, Lawrence Severt, Vicki Shanker, Ann L. Hunt, Susan Bressman, Gregory M. Pastores, Rachel Saunders-Pullman

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)185-186
Number of pages2
JournalJournal of Clinical Neuroscience
Volume28
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Fingerprint

Glucosylceramidase
Parkinson Disease
Mutation
Enzymes
Gaucher Disease

Keywords

  • Biomarker
  • Gaucher
  • GBA
  • GBA enzyme activity
  • Glucocerebrosidase
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Physiology (medical)

Cite this

Ortega, R. A., Torres, P. A., Swan, M., Nichols, W., Boschung, S., Raymond, D., ... Saunders-Pullman, R. (2016). Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease. Journal of Clinical Neuroscience, 28, 185-186. https://doi.org/10.1016/j.jocn.2015.12.004

Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease. / Ortega, Roberto A.; Torres, Paola A.; Swan, Matthew; Nichols, William; Boschung, Sarah; Raymond, Deborah; Barrett, Matthew J.; Johannes, Brooke A.; Severt, Lawrence; Shanker, Vicki; Hunt, Ann L.; Bressman, Susan; Pastores, Gregory M.; Saunders-Pullman, Rachel.

In: Journal of Clinical Neuroscience, Vol. 28, 01.06.2016, p. 185-186.

Research output: Contribution to journalArticle

Ortega, RA, Torres, PA, Swan, M, Nichols, W, Boschung, S, Raymond, D, Barrett, MJ, Johannes, BA, Severt, L, Shanker, V, Hunt, AL, Bressman, S, Pastores, GM & Saunders-Pullman, R 2016, 'Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease', Journal of Clinical Neuroscience, vol. 28, pp. 185-186. https://doi.org/10.1016/j.jocn.2015.12.004
Ortega RA, Torres PA, Swan M, Nichols W, Boschung S, Raymond D et al. Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease. Journal of Clinical Neuroscience. 2016 Jun 1;28:185-186. https://doi.org/10.1016/j.jocn.2015.12.004
Ortega, Roberto A. ; Torres, Paola A. ; Swan, Matthew ; Nichols, William ; Boschung, Sarah ; Raymond, Deborah ; Barrett, Matthew J. ; Johannes, Brooke A. ; Severt, Lawrence ; Shanker, Vicki ; Hunt, Ann L. ; Bressman, Susan ; Pastores, Gregory M. ; Saunders-Pullman, Rachel. / Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease. In: Journal of Clinical Neuroscience. 2016 ; Vol. 28. pp. 185-186.
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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.",
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