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

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...

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Autores principales: Mielke, Michelle M., Maetzler, Walter, Haughey, Norman J., Bandaru, Veera V. R., Savica, Rodolfo, Deuschle, Christian, Gasser, Thomas, Hauser, Ann-Kathrin, Gräber-Sultan, Susanne, Schleicher, Erwin, Berg, Daniela, Liepelt-Scarfone, Inga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776817/
https://www.ncbi.nlm.nih.gov/pubmed/24058461
http://dx.doi.org/10.1371/journal.pone.0073094
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author Mielke, Michelle M.
Maetzler, Walter
Haughey, Norman J.
Bandaru, Veera V. R.
Savica, Rodolfo
Deuschle, Christian
Gasser, Thomas
Hauser, Ann-Kathrin
Gräber-Sultan, Susanne
Schleicher, Erwin
Berg, Daniela
Liepelt-Scarfone, Inga
author_facet Mielke, Michelle M.
Maetzler, Walter
Haughey, Norman J.
Bandaru, Veera V. R.
Savica, Rodolfo
Deuschle, Christian
Gasser, Thomas
Hauser, Ann-Kathrin
Gräber-Sultan, Susanne
Schleicher, Erwin
Berg, Daniela
Liepelt-Scarfone, Inga
author_sort Mielke, Michelle M.
collection PubMed
description 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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spelling pubmed-37768172013-09-20 Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study Mielke, Michelle M. Maetzler, Walter Haughey, Norman J. Bandaru, Veera V. R. Savica, Rodolfo Deuschle, Christian Gasser, Thomas Hauser, Ann-Kathrin Gräber-Sultan, Susanne Schleicher, Erwin Berg, Daniela Liepelt-Scarfone, Inga PLoS One Research Article 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. Public Library of Science 2013-09-18 /pmc/articles/PMC3776817/ /pubmed/24058461 http://dx.doi.org/10.1371/journal.pone.0073094 Text en © 2013 Mielke et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mielke, Michelle M.
Maetzler, Walter
Haughey, Norman J.
Bandaru, Veera V. R.
Savica, Rodolfo
Deuschle, Christian
Gasser, Thomas
Hauser, Ann-Kathrin
Gräber-Sultan, Susanne
Schleicher, Erwin
Berg, Daniela
Liepelt-Scarfone, Inga
Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study
title Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study
title_full Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study
title_fullStr Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study
title_full_unstemmed Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study
title_short Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study
title_sort plasma ceramide and glucosylceramide metabolism is altered in sporadic parkinson's disease and associated with cognitive impairment: a pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776817/
https://www.ncbi.nlm.nih.gov/pubmed/24058461
http://dx.doi.org/10.1371/journal.pone.0073094
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