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Borkowski, K.* ; Seyfried, N.T.* ; Arnold, M. ; Lah, J.J.* ; Levey, A.I.* ; Hales, C.M.* ; Dammer, E.B.* ; Blach, C.* ; Louie, G.* ; Kaddurah-Daouk, R.* ; Newman, J.W.*

Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism.

Sci. Rep. 13:13752 (2023)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Soluble Epoxide Hydrolase; Alzheimers-disease; Bile-acid; Endocannabinoid System; Inhibition; Deficiency; Oxylipins; Stress; Liver; Pain

ISSN (print) / ISBN 2045-2322

e-ISSN 2045-2322

Journal Scientific Reports

Quellenangaben Volume: 13, Issue: 1, Article Number: 13752

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants Cognitive Neurology Research
Alzheimer's Disease Metabolomics Consortium (ADMC)
Alzheimer's Disease Metabolomics Consortium
Emory Healthy Brain Study
National Institute on Aging (NIA)
FNIH
NIA
Emory ADRC
USDA