Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study

Michelle M. Mielke, 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

Research output: Contribution to journalArticle

81 Scopus citations

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.

Original languageEnglish (US)
Article numbere73094
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 18 2013

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Mielke, M. M., Maetzler, W., Haughey, N. J., Bandaru, V. V. R., Savica, R., Deuschle, C., Gasser, T., Hauser, A. K., Gräber-Sultan, S., Schleicher, E., Berg, D., & Liepelt-Scarfone, I. (2013). Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study. PloS one, 8(9), [e73094]. https://doi.org/10.1371/journal.pone.0073094