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

doi:10.1002/mds.28792

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 journal › Article › peer-review

21 Scopus citations

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 language	English
Pages (from-to)	190-195
Number of pages	6
Journal	Movement Disorders
Volume	37
Issue number	1
DOIs	https://doi.org/10.1002/mds.28792
State	Published - Jan 2022

Funding

Funders	Funder 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 Genzyme	TLV-0204-16
Israel Science Foundation
Tel Aviv Sourasky Medical Center
Sagol School of Neuroscience, Tel Aviv University

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10.1002/mds.28792

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Omer, N., Giladi, N., Gurevich, T., Bar-Shira, A., Gana-Weisz, M., Glinka, T., Goldstein, O., Kestenbaum, M., Cedarbaum, J. M., Mabrouk, O. S., Fraser, K. B., Shirvan, J. C., Orr-Urtreger, A., Mirelman, A., & Thaler, A. (2022). Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity. Movement Disorders, 37(1), 190-195. https://doi.org/10.1002/mds.28792

@article{00de9a7f0b7b4a6ea310134d8e6b54aa,

title = "Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society",

year = "2022",

month = jan,

doi = "10.1002/mds.28792",

language = "אנגלית",

volume = "37",

pages = "190--195",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley and Sons Inc.",

number = "1",

}

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 2022, 'Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity', Movement Disorders, vol. 37, no. 1, pp. 190-195. https://doi.org/10.1002/mds.28792

TY - JOUR

T1 - Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity

AU - Omer, Nurit

AU - Giladi, Nir

AU - Gurevich, Tanya

AU - Bar-Shira, Anat

AU - Gana-Weisz, Mali

AU - Glinka, Tal

AU - Goldstein, Orly

AU - Kestenbaum, Meir

AU - Cedarbaum, Jesse M.

AU - Mabrouk, Omar S.

AU - Fraser, Kyle B.

AU - Shirvan, Julia C.

AU - Orr-Urtreger, Avi

AU - Mirelman, Anat

AU - Thaler, Avner

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

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DO - 10.1002/mds.28792

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C2 - 34550621

AN - SCOPUS:85115273442

SN - 0885-3185

VL - 37

SP - 190

EP - 195

JO - Movement Disorders

JF - Movement Disorders

IS - 1

ER -

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

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