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. 2021;80(3):1221-1229.
doi: 10.3233/JAD-201295.

The Effect of GBA Mutations and APOE Polymorphisms on Dementia with Lewy Bodies in Ashkenazi Jews

Tamara Shiner  1   2   3   4 , Anat Mirelman  2   3   5 , Yevgenia Rosenblum  1   2   5 , Gitit Kavé  1   6 , Mali Gana Weisz  7 , Anat Bar-Shira  7 , Orly Goldstein  7 , Avner Thaler  2   3   4   5 , Tanya Gurevich  2   3   4 , Avi Orr-Urtreger  2   3   7 , Nir Giladi  2   3   4   5 , Noa Bregman  1   2
Affiliations

The Effect of GBA Mutations and APOE Polymorphisms on Dementia with Lewy Bodies in Ashkenazi Jews

Tamara Shiner et al. J Alzheimers Dis. 2021.

Abstract

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 ɛ4 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 ɛ4 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 ɛ4 allele among AJ patients with DLB, both of which have distinct effects on the clinical disease phenotype, separately and in combination.

Keywords: Apolipoprotein; Lewy body disease; dementia; glucocerebrosidase; parkinsonism.

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Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/20-1295r3).

Figures

Fig. 1
Fig. 1
Effect of GBA mutations and APOE ɛ4 polymorphisms on MMSE, UPDRS, and MOCA scores. MMSE interaction effect; p = 0.046. MOCA interaction effect; p = 0.210. UPDRS interaction effect; p = 0.037.
See this image and copyright information in PMC

References

    1. McKeith IG (2000) Spectrum of Parkinson’s disease, Parkinson’s dementia, and Lewy body dementia. Neurol Clin 18, 865–902. - PubMed
    1. Halliday GM, Holton JL, Revesz T, Dickson DW (2011) Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol (Berl) 122, 187–204. - PubMed
    1. Tiraboschi P, Attems J, Thomas A, Brown A, Jaros E, Lett DJ, Ossola M, Perry RH, Ramsay L, Walker L, McKeith IG (2015) Clinicians’ ability to diagnose dementia with Lewy bodies is not affected by β-amyloid load. Neurology 84, 496–499. - PMC - PubMed
    1. Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM, Theuns J, Crosiers D, Cras P, Engelborghs S, De Deyn PP, Van Broeckhoven C, Mann DM, Snowden J, Pickering-Brown S, Halliwell N, Davidson Y, Gibbons L, Harris J, Sheerin UM, Bras J, Hardy J, Clark L, Marder K, Honig LS, Berg D, Maetzler W, Brockmann K, Gasser T, Novellino F, Quattrone A, Annesi G, De Marco EV, Rogaeva E, Masellis M, Black SE, Bilbao JM, Foroud T, Ghetti B, Nichols WC, Pankratz N, Halliday G, Lesage S, Klebe S, Durr A, Duyckaerts C, Brice A, Giasson BI, Trojanowski JQ, Hurtig HI, Tayebi N, Landazabal C, Knight MA, Keller M, Singleton AB, Wolfsberg TG, Sidransky E (2013) A multicenter study of glucocerebrosidase mutations in dementia with lewy bodies. JAMA Neurol 70, 727–735. - PMC - PubMed
    1. Mata IF, Samii A, Schneer SH, Roberts JW, Griffith A, Leis BC, Schellenberg GD, Sidransky E, Bird TD, Leverenz JB, Tsuang D, Zabetian CP (2008) Glucocerebrosidase gene mutations: A risk factor for Lewy body disorders. Arch Neurol 65, 379–382. - PMC - PubMed