The effect of GBA Mutations and APOE polymorphisms on dementia with lewy bodies in ashkenazi jews

Tamara Shiner, Anat Mirelman, Yevgenia Rosenblum, Gitit Kavé, Mali Gana Weisz, Anat Bar-Shira, Orly Goldstein, Avner Thaler, Tanya Gurevich, Avi Orr-Urtreger, Nir Giladi, Noa Bregman

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: Glucocerebrosidase (GBA) gene mutations and APOE polymorphisms are common in dementia with Lewy bodies (DLB), however their clinical impact is only partially elucidated. Objective: To explore the clinical impact of mutations in the GBA gene and APOE polymorphisms separately and in combination, in a cohort of Ashkenazi Jewish (AJ) patients with DLB. Methods: One hundred consecutively recruited AJ patients with clinically diagnosed DLB underwent genotyping for GBA mutations and APOE polymorphisms, and performed cognitive and motor clinical assessments. Results: Thirty-two (32%) patients with DLB were carriers of GBA mutations and 33 (33%) carried an APOE ϵ4 allele. GBA mutation carriers had a younger age of onset (mean [SD] age, 67.2 years [8.9] versus 71.97 [5.91]; p = 0.03), poorer cognition as assessed by the Mini-Mental State Examination (21.41 [6.9] versus 23.97 [5.18]; p < 0.005), and more severe parkinsonism as assessed with the Unified Parkinson's Disease Rating Scale motor part III (34.41 [13.49] versus 28.38 [11.21]; p = 0.01) compared to non-carriers. There were statistically significant interactions between the two genetic factors, so that patients who carried both a mild GBA mutation and the APOE ϵ4 allele (n = 9) had more severe cognitive (p = 0.048) and motor dysfunction (p = 0.037). Conclusion: We found a high frequency of both GBA mutations and the APOE ϵ4 allele among AJ patients with DLB, both of which have distinct effects on the clinical disease phenotype, separately and in combination.

Original languageEnglish
Pages (from-to)1221-1229
Number of pages9
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 1 Jan 2021
Externally publishedYes


  • Apolipoprotein
  • Dementia
  • Glucocerebrosidase
  • Lewy body disease
  • Parkinsonism

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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