Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism
Abstract Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer’s disease. Using metabolomics, we have previously profiled oxylipins, endocannabinoids, bile acids, and steroids...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39737-8 |
| _version_ | 1797577054110089216 |
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| author | Kamil Borkowski Nicholas T. Seyfried Matthias Arnold James J. Lah Allan I. Levey Chadwick M. Hales Eric B. Dammer Colette Blach Gregory Louie Rima Kaddurah-Daouk John W. Newman |
| author_facet | Kamil Borkowski Nicholas T. Seyfried Matthias Arnold James J. Lah Allan I. Levey Chadwick M. Hales Eric B. Dammer Colette Blach Gregory Louie Rima Kaddurah-Daouk John W. Newman |
| author_sort | Kamil Borkowski |
| collection | DOAJ |
| description | Abstract Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer’s disease. Using metabolomics, we have previously profiled oxylipins, endocannabinoids, bile acids, and steroids in 293 CSF and 202 matched plasma samples from AD cases and healthy controls and identified both central and peripheral markers of AD pathology within inflammation-regulating cytochrome p450/soluble epoxide hydrolase pathway. Additionally, using proteomics, we have identified five cerebrospinal fluid protein panels, involved in the regulation of energy metabolism, vasculature, myelin/oligodendrocyte, glia/inflammation, and synapses/neurons, affected in AD, and reflective of AD-related changes in the brain. In the current manuscript, using metabolomics-proteomics data integration, we describe new associations between peripheral and central lipid mediators, with the above-described CSF protein panels. Particularly strong associations were observed between cytochrome p450/soluble epoxide hydrolase metabolites, bile acids, and proteins involved in glycolysis, blood coagulation, and vascular inflammation and the regulators of extracellular matrix. Those metabolic associations were not observed at the gene-co-expression level in the central nervous system. In summary, this manuscript provides new information regarding Alzheimer’s disease, linking both central and peripheral metabolism, and illustrates the necessity for the “omics” data integration to uncover associations beyond gene co-expression. |
| first_indexed | 2024-03-10T22:02:29Z |
| format | Article |
| id | doaj.art-8bf68a11806b4e5a948a71379d7cd203 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T22:02:29Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8bf68a11806b4e5a948a71379d7cd2032023-11-19T12:54:13ZengNature PortfolioScientific Reports2045-23222023-08-0113111310.1038/s41598-023-39737-8Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolismKamil Borkowski0Nicholas T. Seyfried1Matthias Arnold2James J. Lah3Allan I. Levey4Chadwick M. Hales5Eric B. Dammer6Colette Blach7Gregory Louie8Rima Kaddurah-Daouk9John W. Newman10West Coast Metabolomics Center, Genome Center, University of California DavisDepartment of Biochemistry, Emory University School of MedicineInstitute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental HealthDepartment of Neurology, Emory UniversityDepartment of Neurology, Emory UniversityDepartment of Neurology, Emory UniversityDepartment of Biochemistry, Emory University School of MedicineDuke Molecular Physiology Institute, Duke UniversityDepartment of Psychiatry and Behavioral Sciences, Duke UniversityDepartment of Psychiatry and Behavioral Sciences, Duke UniversityWest Coast Metabolomics Center, Genome Center, University of California DavisAbstract Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer’s disease. Using metabolomics, we have previously profiled oxylipins, endocannabinoids, bile acids, and steroids in 293 CSF and 202 matched plasma samples from AD cases and healthy controls and identified both central and peripheral markers of AD pathology within inflammation-regulating cytochrome p450/soluble epoxide hydrolase pathway. Additionally, using proteomics, we have identified five cerebrospinal fluid protein panels, involved in the regulation of energy metabolism, vasculature, myelin/oligodendrocyte, glia/inflammation, and synapses/neurons, affected in AD, and reflective of AD-related changes in the brain. In the current manuscript, using metabolomics-proteomics data integration, we describe new associations between peripheral and central lipid mediators, with the above-described CSF protein panels. Particularly strong associations were observed between cytochrome p450/soluble epoxide hydrolase metabolites, bile acids, and proteins involved in glycolysis, blood coagulation, and vascular inflammation and the regulators of extracellular matrix. Those metabolic associations were not observed at the gene-co-expression level in the central nervous system. In summary, this manuscript provides new information regarding Alzheimer’s disease, linking both central and peripheral metabolism, and illustrates the necessity for the “omics” data integration to uncover associations beyond gene co-expression.https://doi.org/10.1038/s41598-023-39737-8 |
| spellingShingle | Kamil Borkowski Nicholas T. Seyfried Matthias Arnold James J. Lah Allan I. Levey Chadwick M. Hales Eric B. Dammer Colette Blach Gregory Louie Rima Kaddurah-Daouk John W. Newman Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism Scientific Reports |
| title | Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism |
| title_full | Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism |
| title_fullStr | Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism |
| title_full_unstemmed | Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism |
| title_short | Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism |
| title_sort | integration of plasma and csf metabolomics with csf proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism |
| url | https://doi.org/10.1038/s41598-023-39737-8 |
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