Objective: We aimed to investigate whether GBA mutations are associated with structural abnormalities in a cohort of GBA mutation carriers with and without manifested PD.

Background: The glucocerebrosidase gene (GBA) encodes for a lysosomal enzyme responsible for the conversion of glucocerebroside into glucose and ceramide and serves as a common risk factor for Parkinson’s disease (PD).

Method: Subcortical structural and white-matter cerebral abnormalities were assessed using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI), respectively, in 86 non-manifesting GBA mutation carriers (GBA-NM), 37 GBA mutation carriers with PD (GBA-PD), 392 idiopathic PD (iPD) patients and 182 Healthy Controls (HC). We compared grey matter volume and mean diffusivity (MD) measurements amongst these groups to determine GBA-specific structural brain changes.

Results: GBA-NM and GBA-PD exhibited increased grey matter volume in the dorsal raphe, midbrain, midbrain reticular formation and pedunculopontine nucleus (P<0.05), compared to HC and iPD, respectively, with GBA-NM and GBA-PD exhibiting reduced MD in the midbrain. GBA-NM demonstrated additional increases of grey matter volume in the hypothalamus, substantia nigra, median raphe and ventral tegmental area (P<0.05), with reduced MD in the hypothalamus and substantia nigra compared to HC.

Conclusion: We demonstrate that GBA gene mutation carriers exhibit increased grey matter volume in subcortical and brainstem regions, which is evident prior to the onset of parkinsonian symptoms. These findings illustrate morphological alterations of GBA-associated parkinsonism. *This abstract was also submitted for presentation at the 2019 European Academy of Neurology conference.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/structural-changes-in-non-manifesting-gba-mutation-carriers-and-gba-mutation-carriers-with-parkinsons-disease/