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

Nurit Omer, Nir Giladi, Tanya Gurevich, Anat Bar-Shira, Mali Gana-Weisz, Tal Glinka, Orly Goldstein, Meir Kestenbaum, Jesse M. Cedarbaum, Omar S. Mabrouk, Kyle B. Fraser, Julia C. Shirvan, Avi Orr-Urtreger, Anat Mirelman, Avner Thaler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)190-195
Number of pages6
JournalMovement Disorders
Volume37
Issue number1
DOIs
StatePublished - Jan 2022

Funding

FundersFunder number
Abbvie Israel
Intec Pharma
Israeli Innovation Authority
LTI
NMNC
NeuroDerm
NeuroDerm Ltd.
Michael J. Fox Foundation for Parkinson's Research
National Parkinson Foundation
Pfizer
Medtronic
Biogen
Teva Pharmaceutical Industries
AbbVie
Allergan
International Parkinson and Movement Disorder Society
Seventh Framework Programme
UCB
Parkinson's Foundation
Sanofi GenzymeTLV-0204-16
Israel Science Foundation
Tel Aviv Sourasky Medical Center
Sagol School of Neuroscience, Tel Aviv University

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