Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

Mov Disord. 2024 Dec;39(12):2280-2285. doi: 10.1002/mds.30003. Epub 2024 Aug 30.

Abstract

Background: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear.

Objective: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status.

Methods: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed.

Results: GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly.

Conclusion: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoproteins E* / genetics
  • Disease Progression*
  • Female
  • Genotype
  • Glucosylceramidase* / genetics
  • Humans
  • Israel
  • Jews* / genetics
  • Lewy Body Disease* / genetics
  • Male
  • Middle Aged
  • Mutation* / genetics
  • Polymorphism, Genetic / genetics

Substances

  • Glucosylceramidase
  • GBA protein, human
  • Apolipoproteins E