Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
Year: 2021
Type: article
Study design: Observational Study
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.
Source: Alzheimer s Research & Therapy
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
Awards: G1249643857, Metabolic Networks and Pathways Predictive of Sex Differences in AD Risk and Responsiveness to Treatment, G160496021, G1665691986, Metabolic Network Analysis of Biochemical Trajectories in Alzheimer's Disease, G2089141579, G231011830, G3188971303, Gut Liver Brain Biochemical Axis in Alzheimer's Disease, G420208702, Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type Dementias, G49689694, Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-AD, G6597655368, G6725792621, Metabolic Networks and Pathways in Alzheimer's Disease, G9000230297, Goizueta Alzheimer's Disease Research Center
OpenAlex ID: W3137459541