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. 2013 Sep 18;8(9):e73094.
doi: 10.1371/journal.pone.0073094. eCollection 2013.

Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson's disease and associated with cognitive impairment: a pilot study

Michelle M Mielke  1 , Walter Maetzler, Norman J Haughey, Veera V R Bandaru, Rodolfo Savica, Christian Deuschle, Thomas Gasser, Ann-Kathrin Hauser, Susanne Gräber-Sultan, Erwin Schleicher, Daniela Berg, Inga Liepelt-Scarfone
Affiliations

Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson's disease and associated with cognitive impairment: a pilot study

Michelle M Mielke et al. PLoS One. .

Abstract

Background: Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide (a monohexosylceramide) into glucose and ceramide, is the most common genetic risk factor for sporadic Parkinson's disease (PD). GBA mutation carriers are more likely to have an earlier age of onset and to develop cognitive impairment and dementia. We hypothesized that plasma levels of lipids involved in ceramide metabolism would also be altered in PD non-GBA mutation carriers and associated with worse cognition.

Methods: Plasma ceramide, monohexosylceramide, and lactosylceramide levels in 26 cognitively normal PD patients, 26 PD patients with cognitive impairment or dementia, and 5 cognitively normal non-PD controls were determined by LC/ESI/MS/MS.

Results: Levels of all lipid species were higher in PD patients versus controls. Among PD patients, levels of ceramide C16:0, C18:0, C20:0, C22:0, and C24:1 and monohexosylceramide C16:0, C20:0 and C24:0 species were higher (all P<0.05) in those with versus without cognitive impairment.

Conclusion: These results suggest that plasma ceramide and monohexosylceramide metabolism is altered in PD non-GBA mutation carriers and that higher levels are associated with worse cognition. Additional studies with larger sample sizes, including cognitively normal controls, are needed to confirm these findings.

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Conflict of interest statement

Competing Interests: Dr. Mielke has consulted for Eli Lilly. Dr. Maetzler received honoraria from GlaxoSmithKline (2011). Dr. Thomas Gasser serves as an editorial board member of Movement Disorders, Parkinsonism and Related Disorders, Journal of Parkinson's Disease and Neurogenetics and is funded by Novartis Pharma. Prof. Gasser received speaker honoraria from Novartis, Merck-Serono, Schwarz Pharma, Boehringer Ingelheim and Valeant Pharma and royalties for his consulting activities from Cefalon Pharma and Merck-Serono. Prof. Gasser holds a patent concerning the LRRK2 gene and neurodegenerative disorders (EP2316927 A3 and US8409809 B2). Dr. Daniela Berg receives funding from Janssen Pharmaceutica, and speaker honoraria from Novartis, GSK, TEVA and Lundbeck. This work was partly supported by an unrestricted grant from Novartis. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Ceramide and glycolipid metabolism.
Products are indicated in bold and italics. Abbreviations for enzymes are as follows: GCase: glucocerebrosidase; GalCer synthase: galactosylceramide synthase; GluCer synthase: glucosylceramide synthase; GalCeramidase: galactosyl ceramidase; LacCer synthase: Lactosylceramide synthase; SMase: Sphingomyelinase; SMS: Sphingomyelin synthase.
See this image and copyright information in PMC

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