Session Information
Date: Tuesday, September 24, 2019
Session Title: Parkinsonisms and Parkinson-Plus
Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: We aimed to explore the frequency and clinical impact of GBA mutations and APOε4 polymorphisms in a cohort of Ashkenazi Jewish (AJ) patients with Dementia with Lewy Bodies (DLB).
Background: DLB is believed to be on a clinico-pathological spectrum between Parkinson’s disease (PD) and Alzheimer’s disease (AD). Mutations in the GBA gene are frequent among DLB and PD patients whereas the APOε4 polymorphism is a significant risk factor for AD but not PD.
Method: 91 AJ patients with DLB, underwent genotyping for the 8 known AJ GBA mutations, APOε polymorphisms and the LRRK2 G2019S mutation. Subjects underwent detailed clinical evaluations.
Results: 32% of DLB patients were carriers of mutations in the GBA gene. 31% of all DLB patients were found to be carrying an APOε4 polymorphism. GBA mutation carriers were younger at symptom onset (66.79 yrs vs 71.02 yrs) and had poorer cognition as assessed by the MOCA (16.76 vs 20.07) and the MMSE (21.73 vs 24.43). GBA mutation carriers were also found to have more severe parkinsonism as assessed by motor UPDRS (34.81 vs 29.01). APOε4 polymorphisms had no significant effect on age of onset of disease or the clinical features of the disease.
Conclusion: We find a high frequency of GBA mutations and APOε4 polymorphisms among AJ patients with DLB compared to the background population prevalence. Furthermore, we find that GBA mutation carriers have a more severe disease phenotype with a younger age of onset, poorer cognition and more severe parkinsonism. Although APOε4 polymorphisms were significantly more frequent among these patients with DLB, their presence was not associated with differences in clinical features. Longitudinal studies on larger groups of patients will be needed to ascertain whether APOε4 polymorphisms have a distinct effect on disease course in DLB.
To cite this abstract in AMA style:
T. Shiner, A. Mirelman, Y. Rozenblum, G. Kave', M. Gana Weisz, A. Bar-Shira, A. Thaler, R. Shahar, T. Gurevich, A. Orr-Urtreger, N. Giladi, N. Bregman. The frequency and impact of mutations in the GBA gene and APOε4 polymorphisms on the clinical features of Dementia with Lewy Bodies among Ashkenazi Jews [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/the-frequency-and-impact-of-mutations-in-the-gba-gene-and-apo%ce%b54-polymorphisms-on-the-clinical-features-of-dementia-with-lewy-bodies-among-ashkenazi-jews/. Accessed June 14, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-frequency-and-impact-of-mutations-in-the-gba-gene-and-apo%ce%b54-polymorphisms-on-the-clinical-features-of-dementia-with-lewy-bodies-among-ashkenazi-jews/