title: No evidence for substrate accumulation in Parkinson brains with GBA mutations.
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.
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Gegg
authors.affiliation: Genzyme, a Sanofi Company, Framingham, Massachusetts, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Sweet
authors.affiliation: Genzyme, a Sanofi Company, Framingham, Massachusetts, USA.
authors.forename: Bing H
authors.initials: BH
authors.lastname: Wang
authors.affiliation: Genzyme, a Sanofi Company, Framingham, Massachusetts, USA.
authors.forename: Lamya S
authors.initials: LS
authors.lastname: Shihabuddin
authors.affiliation: Genzyme, a Sanofi Company, Framingham, Massachusetts, USA.
authors.forename: Sergio Pablo
authors.initials: SP
authors.lastname: Sardi
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D005962:Glucosylceramidase / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011699:Putamen / Q000378:metabolism* / Q000473:pathology; D014015:Tissue Banks; D001617:beta-Glucosidase / Q000235:genetics*
chemical_list: D001617:beta-Glucosidase; D005962:Glucosylceramidase
keywords: Parkinson's disease; glucocerebrosidase; lysosomes; sphingolipids