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.