AI Article Synopsis
- Parkinson's disease (PD) is linked to reduced activity of the glucocerebrosidase (GCase) enzyme, prompting this study to investigate if GCase deficiency leads to the accumulation of its substrate, glucosylceramide (GluCer), in PD brain tissues.
- An advanced UPLC-MS/MS method was created to analyze different GluCer isoforms in brain samples, and the study included 26 PD patients and 18 control samples, assessing GluCer levels at various disease stages.
- Although a trend was noted showing GluCer levels increasing with PD severity, the differences between the sample groups were not statistically significant, possibly due to variability in the data.
Article Abstract
Previous studies demonstrated that Parkinson disease (PD) is associated with a decreased activity of the glucocerebrosidase (GCase) enzyme in brain tissues. The objective of this study was to determine if GCase deficiency is associated with the accumulation of its glucosylceramide (GluCer) substrate in PD brain tissues. An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed, optimized, and validated for the multiplex analysis of GluCer isoforms (C18:0, C20:0, C22:0, C24:1, and C24:0) in brain tissue samples. These molecules were chromatographically separated from their isobaric galactosylceramide (GalCer) counterparts using normal phase chromatography. The analysis was performed by tandem mass spectrometry in the multiple reaction monitoring (MRM) acquisition mode. Limits of detection ranging from 0.4 to 1.1 nmol/g brain tissue were established for the different GluCer isoforms analyzed. For the first time, GluCer isoform levels were analyzed in temporal cortex brain tissue samples from 26 PD patients who were divided into three PD disease stages (IIa, III, and IV) according to the Unified Staging System for Lewy Body Disorders. These specimens were compared with brain tissue samples from 12 controls and 6 patients with Incidental Lewy Body Disease. No significant GluCer concentration differences were observed between the 5 sample groups. The GluCer isoform levels were also normalized with their matching GalCer isoforms. The normalized results showed a trend for GluCer levels which increased with PD severity. However, the differences observed between the groups were not significant, owing likely to the high standard deviations measured.
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| http://dx.doi.org/10.1021/acs.analchem.5b04227 | DOI Listing |
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