Importance: Dementia with Lewy bodies (DLB) is a neurodegenerative disease linked to abnormal accumulation of phosphorylated α-synuclein. GBA1 is the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), whose mutations are a risk factor of DLB.
Objective: To report all available data exploring the association between GBA1 mutations and DLB.
Evidence review: All publications focused on GCase and DLB in humans between 2003 and 2022 were identified on PubMed, Cochrane and ClinicalTrials.gov.
Findings: 29 studies were included and confirmed the strong association between GBA1 mutations and DLB (Odds Ratio [OR]: 8.28). GBA1 mutation carriers presented a more malignant phenotype, with earlier symptom onset, more severe motor and cognitive dysfunctions, more visual hallucinations and rapid eye movement sleep disorder. GBA1 mutations were associated with "purer" neuropathological DLB. No therapeutic recommendations exist and clinical trials targeting GCase are just starting in DLB patients.
Conclusions and relevance: This review reports a link between GBA1 mutations and the DLB phenotype with limited evidence due to the small number of studies.
Keywords: Dementia with Lewy bodies; GBA1 gene; Gaucher disease; Glucocerebrosidase.
Copyright © 2022. Published by Elsevier Ltd.