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

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 - 1 Jan 2022
Externally published	Yes

ASJC Scopus subject areas

Neurology
Clinical Neurology

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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{d9d44d67a2444818b5e434ca4d6a8f72,

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,

day = "1",

doi = "10.1002/mds.28792",

language = "English",

volume = "37",

pages = "190--195",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley and Sons Inc.",

number = "1",

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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 - 2022/1/1

Y1 - 2022/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85115273442&partnerID=8YFLogxK

U2 - 10.1002/mds.28792

DO - 10.1002/mds.28792

M3 - Article

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

Abstract

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