Metabolomic characterization of normal aging and Alzheimer's disease under anesthesia- surgery stimuli

我们建议通过体外和体内实验来量化衰老和AD相关的脑和血液代谢变化。 在促进AD刺激、麻醉-手术、 不管有没有预防性、保护性的治疗。这种方法认识到AD的发病、发病机制和 进展必须导致大脑和其他组织的整体代谢状态或代谢组学的变化 AD患者的器官，与健康人的正常稳态相比，以及我们对 迫切需要开发非侵入性AD诊断工具。在提出的三个目标中，我们将：(1) 利用不同脑区和血液的组织体外研究与年龄相关的代谢变化 野生型和AD小鼠麻醉-手术刺激后的血清；(2) 多模式在体MR无创评估年龄和AD相关的脑代谢 麻醉-手术刺激引起的变化；以及(3)研究AD保护性干预的效果 麻醉-手术刺激给药后代谢变化的研究。这个项目的成功将 引导我们建立可指导和解释体内多模式磁共振成像结果的翻译方案 通过在所提出的动物模型中获得准确的体外MRS、EM和免疫化学测量， 并将这些发现转化为临床方案，用于人类AD的非侵入性诊断。

We propose to quantify aging- and AD-associated brain and blood metabolic changes through ex vivo and in vivo multimodality MR measurements in mouse models after an AD-promoting stimuli, anesthesia-surgery, with-or-without preventive, protective treatments. This approach recognizes that AD onset, pathogenesis and progression must produce alterations in the overall metabolic status, or metabolomics, of brain and other organs in AD patients, as compared with normal homeostasis in healthy individuals, and our understanding of the urgent need to develop non-invasive AD diagnosis tools. In the three proposed Aims, we will (1) Characterize age-associated metabolomic changes ex vivo using tissues from different brain regions and blood serum obtained from wild-type and AD mice after administration of anesthesia-surgery stimuli; (2) Develop multimodality in vivo MR protocols for non-invasive evaluations of age- and AD-associated brain metabolic changes induced by anesthesia-surgery stimuli; and (3) Investigate the effect of an AD protective intervention on metabolomic changes after administration of anesthesia-surgery stimuli. The success of this project will lead us to establish translational protocols that can guide and interpret multimodality in vivo MR imaging results by obtaining accurate ex vivo MRS, EM, and immunochemistry measurements in the proposed animal models, and translating these findings into clinical protocols for human AD non-invasive diagnosis.