التفاصيل البيبلوغرافية
| العنوان: |
Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease |
| المؤلفون: |
Borkowski, Kamil, Pedersen, Theresa L, Seyfried, Nicholas T, Lah, James J, Levey, Allan I, Hales, Chadwick M, Dammer, Eric B, Blach, Colette, Louie, Gregory, Kaddurah-Daouk, Rima, Newman, John W |
| المصدر: |
Alzheimer's Research & Therapy, vol 13, iss 1 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2021 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Aging, Acquired Cognitive Impairment, Alzheimer's Disease, Brain Disorders, Dementia, Neurosciences, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Alzheimer Disease, Cytochrome P-450 Enzyme System, Epoxide Hydrolases, Fatty Acids, Humans, Oxylipins, Lipid mediators, Endocannabinoids, Cognition, Alzheimer’s Disease Metabolomics Consortium, Alzheimer’s disease, Medical and Health Sciences, Health sciences |
| الوصف: |
BackgroundAlzheimer'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.MethodsLipid 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.ResultsIn 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.ConclusionsPrevious 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. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt2pz4q6g7; https://escholarship.org/uc/item/2pz4q6g7Test |
| الإتاحة: |
https://escholarship.org/uc/item/2pz4q6g7Test |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.960AD49D |
| قاعدة البيانات: |
BASE |
