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. 2015 Jul;30(8):1085-9.
doi: 10.1002/mds.26278. Epub 2015 Jun 11.

No evidence for substrate accumulation in Parkinson brains with GBA mutations

Matthew E Gegg  1 , Lindsay Sweet  2 , Bing H Wang  2 , Lamya S Shihabuddin  2 , Sergio Pablo Sardi  2 , Anthony H V Schapira  1
Affiliations

No evidence for substrate accumulation in Parkinson brains with GBA mutations

Matthew E Gegg et al. Mov Disord. 2015 Jul.

Abstract

Background: To establish whether Parkinson's disease (PD) brains previously described to have decreased glucocerebrosidase activity exhibit accumulation of the lysosomal enzyme's substrate, glucosylceramide, or other changes in lipid composition.

Methods: Lipidomic analyses and cholesterol measurements were performed on the putamen (n = 5-7) and cerebellum (n = 7-14) of controls, Parkinson's disease brains with heterozygote GBA1 mutations (PD+GBA), or sporadic PD.

Results: Total glucosylceramide levels were unchanged in both PD+GBA and sporadic PD brains when compared with controls. No changes in glucosylsphingosine (deacetylated glucosylceramide), sphingomyelin, gangliosides (GM2, GM3), or total cholesterol were observed in either putamen or cerebellum.

Conclusions: This study did not demonstrate glucocerebrosidase substrate accumulation in PD brains with heterozygote GBA1 mutations in areas of the brain with low α-synuclein pathology.

Keywords: Parkinson's disease; glucocerebrosidase; lysosomes; sphingolipids.

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Figures

Figure 1
Figure 1
Plot of GCase activity against GlcCer levels for control, PD+GBA, and PD samples in putamen (A) and cerebellum (B). Relationship between GCase activity4 and GlcCer for each heterozygote GBA mutation is shown in the right panel. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
See this image and copyright information in PMC

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