Category: Parkinson's Disease: Pathophysiology
Objective: To investigate whether post-translational modifications of α-synuclein will give rise to species that differ between PD cases with N370S GBA mutation and WT-PD.
Background: Glucocerebrosidase (GBA) mutations are a recognized risk factor for developing not only Parkinson’s disease (PD) but also Lewy body dementia (LBD), including dementia with Lewy body (DLB), and PD dementia (PDD). Currently, there is no clear understanding of the mechanistic relationships between GBA mutations and α-synuclein accumulation, although, GBA mutations are thought to accelerate α-synuclein accumulation.
Method: 14 PD/LBD cases with and without GBA N370S were obtained from QSBB and 2 from SWBB. Brain regions of anterior cingulate cortex (ACC), substantia nigra (SN), and ventral tegmental area (VTA) were examined using immunohistochemistry with 5 different α-synuclein antibodies: 4 novel epitopes at the n-and c-terminal of a-synuclein and 1 well-known phosphorylation site and analysed semiquantitatively using the modified version of Mckeith criteria.
Results: In cingulate cortex, although, Lewy body (LB) inclusions were higher in N370S PD/LBD compared with WT PD/LBD, a significant difference was found only with the n-terminal antibody. In SN, LB-pathology was increased in the GBA group compared with WT-PD. In VTA, several different structures including LBs, pale bodies, and cytoplasmic staining were significantly higher in the GBA group compared with WT-PD using different antibodies employed in this study.
Conclusion: Immunohistochemical results suggest that N370S GBA mutation exacerbate α-syn pathology. These findings may explain why clinically, GBA mutation carriers manifest early disease onset, increased cognitive decline, and rapid disease progression compared to non-carriers.
To cite this abstract in AMA style:T. Eid. GBA Mutation Accumulates Higher Alpha-Synuclein in Alpha-Synucleinopathies [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/gba-mutation-accumulates-higher-alpha-synuclein-in-alpha-synucleinopathies/. Accessed December 7, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/gba-mutation-accumulates-higher-alpha-synuclein-in-alpha-synucleinopathies/