No evidence for substrate accumulation in Parkinson brains with GBA mutations

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. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.