No evidence for substrate accumulation in Parkinson brains with GBA mutations

• Published in: Movement disorders Vol. 30; no. 8; pp. 1085 - 1089
• Main Authors: Gegg, Matthew E., Sweet, Lindsay, Wang, Bing H., Shihabuddin, Lamya S., Sardi, Sergio Pablo, Schapira, Anthony H.V.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2015; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: beta-Glucosidase - genetics; Cerebellum - metabolism; Cerebellum - pathology; glucocerebrosidase; Glucosylceramidase - metabolism; Humans; lysosomes; Movement disorders; Mutation; Parkinson's disease; Putamen - metabolism; Putamen - pathology; sphingolipids; Tissue Banks; lysosomes; Parkinson's disease; sphingolipids; glucocerebrosidase
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.26278

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.