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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3776817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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