Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease

Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Kamil Borkowski [verfasserIn] Theresa L. Pedersen [verfasserIn] Nicholas T. Seyfried [verfasserIn] James J. Lah [verfasserIn] Allan I. Levey [verfasserIn] Chadwick M. Hales [verfasserIn] Eric B. Dammer [verfasserIn] Colette Blach [verfasserIn] Gregory Louie [verfasserIn] Rima Kaddurah-Daouk [verfasserIn] John W. Newman [verfasserIn] Alzheimer’s Disease Metabolomics Consortium [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition

Übergeordnetes Werk:	In: Alzheimer’s Research & Therapy - BMC, 2015, 13(2021), 1, Seite 16
Übergeordnetes Werk:	volume:13 ; year:2021 ; number:1 ; pages:16

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13195-021-00893-6

Katalog-ID:	DOAJ057956200

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520			\|a Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease.
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650		4	\|a Lipid mediators
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653		0	\|a Neurosciences. Biological psychiatry. Neuropsychiatry
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allfields	10.1186/s13195-021-00893-6 doi (DE-627)DOAJ057956200 (DE-599)DOAJbcf375c3714c4dea8ad067a66582b178 DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Kamil Borkowski verfasserin aut Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease. Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Theresa L. Pedersen verfasserin aut Nicholas T. Seyfried verfasserin aut James J. Lah verfasserin aut Allan I. Levey verfasserin aut Chadwick M. Hales verfasserin aut Eric B. Dammer verfasserin aut Colette Blach verfasserin aut Gregory Louie verfasserin aut Rima Kaddurah-Daouk verfasserin aut John W. Newman verfasserin aut Alzheimer’s Disease Metabolomics Consortium verfasserin aut In Alzheimer’s Research & Therapy BMC, 2015 13(2021), 1, Seite 16 (DE-627)605683557 (DE-600)2506521-X 17589193 nnns volume:13 year:2021 number:1 pages:16 https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/article/bcf375c3714c4dea8ad067a66582b178 kostenfrei https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/toc/1758-9193 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 1 16
spelling	10.1186/s13195-021-00893-6 doi (DE-627)DOAJ057956200 (DE-599)DOAJbcf375c3714c4dea8ad067a66582b178 DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Kamil Borkowski verfasserin aut Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease. Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Theresa L. Pedersen verfasserin aut Nicholas T. Seyfried verfasserin aut James J. Lah verfasserin aut Allan I. Levey verfasserin aut Chadwick M. Hales verfasserin aut Eric B. Dammer verfasserin aut Colette Blach verfasserin aut Gregory Louie verfasserin aut Rima Kaddurah-Daouk verfasserin aut John W. Newman verfasserin aut Alzheimer’s Disease Metabolomics Consortium verfasserin aut In Alzheimer’s Research & Therapy BMC, 2015 13(2021), 1, Seite 16 (DE-627)605683557 (DE-600)2506521-X 17589193 nnns volume:13 year:2021 number:1 pages:16 https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/article/bcf375c3714c4dea8ad067a66582b178 kostenfrei https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/toc/1758-9193 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 1 16
allfields_unstemmed	10.1186/s13195-021-00893-6 doi (DE-627)DOAJ057956200 (DE-599)DOAJbcf375c3714c4dea8ad067a66582b178 DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Kamil Borkowski verfasserin aut Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease. Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Theresa L. Pedersen verfasserin aut Nicholas T. Seyfried verfasserin aut James J. Lah verfasserin aut Allan I. Levey verfasserin aut Chadwick M. Hales verfasserin aut Eric B. Dammer verfasserin aut Colette Blach verfasserin aut Gregory Louie verfasserin aut Rima Kaddurah-Daouk verfasserin aut John W. Newman verfasserin aut Alzheimer’s Disease Metabolomics Consortium verfasserin aut In Alzheimer’s Research & Therapy BMC, 2015 13(2021), 1, Seite 16 (DE-627)605683557 (DE-600)2506521-X 17589193 nnns volume:13 year:2021 number:1 pages:16 https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/article/bcf375c3714c4dea8ad067a66582b178 kostenfrei https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/toc/1758-9193 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 1 16
allfieldsGer	10.1186/s13195-021-00893-6 doi (DE-627)DOAJ057956200 (DE-599)DOAJbcf375c3714c4dea8ad067a66582b178 DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Kamil Borkowski verfasserin aut Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease. Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Theresa L. Pedersen verfasserin aut Nicholas T. Seyfried verfasserin aut James J. Lah verfasserin aut Allan I. Levey verfasserin aut Chadwick M. Hales verfasserin aut Eric B. Dammer verfasserin aut Colette Blach verfasserin aut Gregory Louie verfasserin aut Rima Kaddurah-Daouk verfasserin aut John W. Newman verfasserin aut Alzheimer’s Disease Metabolomics Consortium verfasserin aut In Alzheimer’s Research & Therapy BMC, 2015 13(2021), 1, Seite 16 (DE-627)605683557 (DE-600)2506521-X 17589193 nnns volume:13 year:2021 number:1 pages:16 https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/article/bcf375c3714c4dea8ad067a66582b178 kostenfrei https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/toc/1758-9193 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 1 16
allfieldsSound	10.1186/s13195-021-00893-6 doi (DE-627)DOAJ057956200 (DE-599)DOAJbcf375c3714c4dea8ad067a66582b178 DE-627 ger DE-627 rakwb eng RC321-571 RC346-429 Kamil Borkowski verfasserin aut Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease. Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system Theresa L. Pedersen verfasserin aut Nicholas T. Seyfried verfasserin aut James J. Lah verfasserin aut Allan I. Levey verfasserin aut Chadwick M. Hales verfasserin aut Eric B. Dammer verfasserin aut Colette Blach verfasserin aut Gregory Louie verfasserin aut Rima Kaddurah-Daouk verfasserin aut John W. Newman verfasserin aut Alzheimer’s Disease Metabolomics Consortium verfasserin aut In Alzheimer’s Research & Therapy BMC, 2015 13(2021), 1, Seite 16 (DE-627)605683557 (DE-600)2506521-X 17589193 nnns volume:13 year:2021 number:1 pages:16 https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/article/bcf375c3714c4dea8ad067a66582b178 kostenfrei https://doi.org/10.1186/s13195-021-00893-6 kostenfrei https://doaj.org/toc/1758-9193 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 1 16
language	English
source	In Alzheimer’s Research & Therapy 13(2021), 1, Seite 16 volume:13 year:2021 number:1 pages:16
sourceStr	In Alzheimer’s Research & Therapy 13(2021), 1, Seite 16 volume:13 year:2021 number:1 pages:16
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition Neurosciences. Biological psychiatry. Neuropsychiatry Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Alzheimer’s Research & Therapy
authorswithroles_txt_mv	Kamil Borkowski @@aut@@ Theresa L. Pedersen @@aut@@ Nicholas T. Seyfried @@aut@@ James J. Lah @@aut@@ Allan I. Levey @@aut@@ Chadwick M. Hales @@aut@@ Eric B. Dammer @@aut@@ Colette Blach @@aut@@ Gregory Louie @@aut@@ Rima Kaddurah-Daouk @@aut@@ John W. Newman @@aut@@ Alzheimer’s Disease Metabolomics Consortium @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	605683557
id	DOAJ057956200
language_de	englisch
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callnumber-first	R - Medicine
author	Kamil Borkowski
spellingShingle	Kamil Borkowski misc RC321-571 misc RC346-429 misc Alzheimer’s disease misc Lipid mediators misc Oxylipins misc Endocannabinoids misc Cognition misc Neurosciences. Biological psychiatry. Neuropsychiatry misc Neurology. Diseases of the nervous system Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
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topic_title	RC321-571 RC346-429 Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease Alzheimer’s disease Lipid mediators Oxylipins Endocannabinoids Cognition
topic	misc RC321-571 misc RC346-429 misc Alzheimer’s disease misc Lipid mediators misc Oxylipins misc Endocannabinoids misc Cognition misc Neurosciences. Biological psychiatry. Neuropsychiatry misc Neurology. Diseases of the nervous system
topic_unstemmed	misc RC321-571 misc RC346-429 misc Alzheimer’s disease misc Lipid mediators misc Oxylipins misc Endocannabinoids misc Cognition misc Neurosciences. Biological psychiatry. Neuropsychiatry misc Neurology. Diseases of the nervous system
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title	Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
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title_full	Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
author_sort	Kamil Borkowski
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author_browse	Kamil Borkowski Theresa L. Pedersen Nicholas T. Seyfried James J. Lah Allan I. Levey Chadwick M. Hales Eric B. Dammer Colette Blach Gregory Louie Rima Kaddurah-Daouk John W. Newman Alzheimer’s Disease Metabolomics Consortium
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title_sort	association of plasma and csf cytochrome p450, soluble epoxide hydrolase, and ethanolamide metabolism with alzheimer’s disease
callnumber	RC321-571
title_auth	Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
abstract	Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease.
abstractGer	Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease.
abstract_unstemmed	Abstract Background Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap. Methods Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression. Results In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively. Conclusions Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease.
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title_short	Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
url	https://doi.org/10.1186/s13195-021-00893-6 https://doaj.org/article/bcf375c3714c4dea8ad067a66582b178 https://doaj.org/toc/1758-9193
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author2Str	Theresa L. Pedersen Nicholas T. Seyfried James J. Lah Allan I. Levey Chadwick M. Hales Eric B. Dammer Colette Blach Gregory Louie Rima Kaddurah-Daouk John W. Newman Alzheimer’s Disease Metabolomics Consortium
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Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease

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