Glucocerebrosidase Mutations and Motor Reserve in Parkinson's Disease

Seok Jong Chung, Phil Hyu Lee, Young H. Sohn, Yun Joong Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Background: The concept of motor reserve explains the individual differences in motor deficits despite similar degrees of nigrostriatal dopamine depletion in Parkinson's disease (PD). Objective: To investigate glucocerebrosidase (GBA) variants as potential determinants of motor reserve for exploratory purposes. Methods: A total of 408 patients with drug-naïve PD were enrolled from the Parkinson's Progression Markers Initiative cohort database. All patients underwent SPECT dopamine transporter (DAT) scans and had results for Sanger sequencing of GBA. Parkinsonian motor deficits were assessed using the Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III). We compared MDS-UPDRS-III scores while adjusting for DAT availability in the putamen (i.e., motor reserve) between the PD groups according to the presence of GBA mutations. Results: Fifty-four (13.2%) patients carried GBA mutations. PD patients with GBA mutations were younger than those without mutations. There were no significant differences in sex, disease duration, years of education, and striatal DAT availability between the PD groups. PD patients with GBA mutations had higher MDS-UPDRS-III scores for the less affected side than those without mutations, despite similar levels of DAT availability in the contralateral putamen. The MDS-UPDRS-III sub-scores of the more affected side did not differ between the two PD groups. Conclusion: The results of this study demonstrated the detrimental effect of GBA variants on individual capacity to cope with PD-related pathologies, with different impacts depending on the motor laterality.

Original languageEnglish
Pages (from-to)1715-1724
Number of pages10
JournalJournal of Parkinson's disease
Issue number4
Publication statusPublished - 2021

Bibliographical note

Funding Information:
Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (http://www.ppmi-info. For up-to-date information on the study, visit PPMI (a public-private partnership) is funded by the Michal J. Fox Foundation for Parkinson’s Research and multiple funding partners, including AbbVie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genetech, The supplementary material is available in the electronic version of this article: 10.3233/JPD-212758.

Publisher Copyright:
© 2021 - IOS Press. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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