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No Evidence for Substrate Accumulation in Parkinson Brains With GBA Mutations

Identifieur interne : 000468 ( Pmc/Corpus ); précédent : 000467; suivant : 000469

No Evidence for Substrate Accumulation in Parkinson Brains With GBA Mutations

Auteurs : Matthew E. Gegg ; Lindsay Sweet ; Bing H. Wang ; Lamya S. Shihabuddin ; Sergio Pablo Sardi ; Anthony H. V. Schapira

Source :

RBID : PMC:4529481

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.


Url:
DOI: 10.1002/mds.26278
PubMed: 26096906
PubMed Central: 4529481

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