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. 2022 Jan;37(1):190-195.
doi: 10.1002/mds.28792. Epub 2021 Sep 22.

Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity

Nurit Omer  1   2   3 , Nir Giladi  1   2   4 , Tanya Gurevich  1   2   4 , Anat Bar-Shira  5 , Mali Gana-Weisz  6 , Tal Glinka  6 , Orly Goldstein  6 , Meir Kestenbaum  2   7 , Jesse M Cedarbaum  8   9 , Omar S Mabrouk  8 , Kyle B Fraser  8 , Julia C Shirvan  8 , Avi Orr-Urtreger  2   6 , Anat Mirelman  2   3   4 , Avner Thaler  1   2   3   4
Affiliations

Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity

Nurit Omer et al. Mov Disord. 2022 Jan.

Abstract

Background: Mutations in the GBA gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are risk factors for Parkinson's disease (PD).

Objective: To explore the association between GCase activity, PD phenotype, and probability for prodromal PD among carriers of mutations in the GBA and LRRK2 genes.

Methods: Participants were genotyped for the G2019S-LRRK2 and nine GBA mutations common in Ashkenazi Jews. Performance-based measures enabling the calculation of the Movement Disorder Society (MDS) prodromal probability score were collected.

Results: One hundred and seventy PD patients (102 GBA-PD, 38 LRRK2-PD, and 30 idiopathic PD) and 221 non-manifesting carriers (NMC) (129 GBA-NMC, 45 LRRK2-NMC, 15 GBA-LRRK2-NMC, and 32 healthy controls) participated in this study. GCase activity was lower among GBA-PD (3.15 ± 0.85 μmol/L/h), GBA-NMC (3.23 ± 0.91 μmol/L/h), and GBA-LRRK2-NMC (3.20 ± 0.93 μmol/L/h) compared to the other groups of participants, with no correlation to clinical phenotype.

Conclusions: Low GCase activity does not explain the clinical phenotype or risk for prodromal PD in this cohort. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: GBA; GCase; LRRK2; Parkinson's disease.

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Figures

FIG. 1
FIG. 1
Glucocerebrosidase (GCase) activity among study subgroups. The line in each box indicates the median, the 95% confidence intervals are displayed as the whiskers, and mean is depicted by the X. P < 0.001. IPD, idiopathic Parkinson's disease; mGBA, mild GBA; sGBA, severe GBA; vGBA, variant GBA; NMC, non‐manifesting carriers; PD, Parkinson's disease. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

Comment in

  • The Jury Is Still Out.
    Lansbury P. Lansbury P. Mov Disord. 2022 Mar;37(3):651. doi: 10.1002/mds.28911. Epub 2022 Jan 17. Mov Disord. 2022. PMID: 35040206 No abstract available.
  • Glucocerebrosidase Activity Is Not Associated with Parkinson's Disease Risk or Severity.
    Omer N, Giladi N, Gurevich T, Bar-Shira A, Gana-Weisz M, Glinka T, Goldstein O, Kestenbaum M, Cedarbaum JM, Mabrouk OS, Fraser KB, Shirvan JC, Orr-Urtreger A, Mirelman A, Thaler A. Omer N, et al. Mov Disord. 2022 Mar;37(3):651-652. doi: 10.1002/mds.28929. Epub 2022 Jan 22. Mov Disord. 2022. PMID: 35064687 No abstract available.

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