Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer's disease.
Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer's disease.
复制标题
DOI：
10.1186/s13195-021-00893-6
复制
发表时间：
2021-09-06
期刊：
影响因子：
--
通讯作者：
Alzheimer’s Disease Metabolomics Consortium
中科院分区：
文献类型：
--
作者：
Borkowski K;Pedersen TL;Seyfried NT;Lah JJ;Levey AI;Hales CM;Dammer EB;Blach C;Louie G;Kaddurah-Daouk R;Newman JW;Alzheimer’s Disease Metabolomics Consortium
阿尔茨海默氏病、心血管疾病和其他心脏代谢紊乱可能有共同的炎症起源。脂质介质，包括氧脂素、内源性大麻素、胆汁酸和类固醇，调节炎症、能量代谢和细胞增殖，在心脏代谢疾病中有明确的参与。然而，它们在阿尔茨海默病中的作用知之甚少。在这里，我们描述了分析血浆和脑脊液脂质介质的病例对照比较约150例阿尔茨海默病患者和135名健康对照，调查这一知识差距。使用靶向定量质谱法测量脂质介质。使用协变量分析对数据进行分析，调整性别、年龄和种族。偏最小二乘判别分析确定血浆和脑脊液脂质介质判别阿尔茨海默病。使用机器学习结合逐步逻辑回归构建阿尔茨海默病预测模型。在血浆和脑脊液中，与健康对照组相比，阿尔茨海默病患者的细胞色素P450/可溶性环氧化物水解酶途径组分升高，脂肪酸乙醇酰胺降低。循环代谢物的可溶性环氧化物水解酶和乙醇酰胺提供阿尔茨海默氏病的预测与接收器操作者的特征曲线范围从0.82到0.92的脑脊液和血浆代谢物，分别与面积。先前的研究报道了阿尔茨海默病相关的可溶性环氧化物水解酶在大脑中的上调，并且内源性大麻素代谢提供了对神经炎症的适应性反应。这项研究支持P450依赖性和内源性大麻素代谢参与阿尔茨海默病。结果进一步表明，针对两种代谢途径的联合药物干预可能对阿尔茨海默病具有治疗益处。在线版本包含补充材料，可通过10.1186/s13195-021-00893-6获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s13195-021-00893-6.
登录
查看更多内容
影响因子：
5.7
作者：
Goetz, Margarethe E.;Hanfelt, John J.;Lah, James J.
通讯作者：
Lah, James J.
影响因子：
5
作者：
Deng Y;Theken KN;Lee CR
通讯作者：
Lee CR
影响因子：
6.5
作者：
Agrawal, Karan;Hassoun, Lauren A.;Newman, John W.
通讯作者：
Newman, John W.
影响因子：
5.6
作者：
Grant SM;DeMorrow S
通讯作者：
DeMorrow S
DOI：
10.1016/j.xcrm.2020.100138
发表时间：
2020-11-17
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Baloni P;Funk CC;Yan J;Yurkovich JT;Kueider-Paisley A;Nho K;Heinken A;Jia W;Mahmoudiandehkordi S;Louie G;Saykin AJ;Arnold M;Kastenmüller G;Griffiths WJ;Thiele I;Alzheimer’s Disease Metabolomics Consortium;Kaddurah-Daouk R;Price ND
通讯作者：
Price ND