SYSTEMATIC REVIEW article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
This article is part of the Research TopicGenetic Underpinnings of Alzheimer's and Parkinson's: Insights and InnovationsView all 5 articles
Effects of glucocerebrosidase gene variations on the risk of Parkinson's disease dementia: a meta-analysis
Provisionally accepted
- Guangxi University of Science and Technology, Liuzhou, China
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Objective: This meta-analysis aimed to investigate the effects of glucocerebrosidase gene (GBA) variations on the risk of Parkinson's disease dementia (PDD) and to identify the relationship between GBA variations and PDD. Method: A comprehensive search was performed to retrieve publications from PubMed, Cochrane Library, Embase and Web of Science up to March 19, 2025. The search terms included "glucocerebrosidase", "Parkinson's disease", and "dementia". After rigorous screening, cohort studies were included for meta-analysis. Results: This meta-analysis revealed a significant overall association between the presence of GBA variation and an increased risk of dementia in PD patients (RR = 1.82, 95% CI: 1.52-2.18, P < 0.00001). When stratified by variant type, carriers of GBA mutations exhibited a similar elevation in dementia risk (RR = 1.82, 95% CI: 1.49-2.23, P < 0.00001), and carriers of GBA polymorphisms also demonstrated a heightened risk (RR = 1.82, 95% CI: 1.26-2.61, P = 0.001). Analysis of specific mutations revealed that the N370S variant was associated with an increase in dementia risk (RR = 1.54, 95% CI: 1.24-1.92, P < 0.0001), whereas the L444P variant conferred a stronger effect (RR = 2.17, 95% CI: 1.74-2.71, P < 0.00001). Additionally, the E326K polymorphism was also significantly associated with an increased risk of dementia (RR = 2.34, 95% CI: 1.88-2.91, P < 0.00001). Conclusion: GBA variations are significant risk factors for PDD, with varying degrees of risk conferred by different variants. These findings underscore the critical role of GBA in the pathogenesis of PDD and highlight its potential as a key genetic risk factor. Trial registration: PROSPERO(CRD420251109378)
Keywords: Glucocerebrosidase, Parkinson's disease, Dementia, Meta-analysis, Gene variations
Received: 23 Jul 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Li, Bi, Yin, Li, Liang, Wu, Quan and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Weiming Liang, liangwm22@icloud.com
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