MRS Metabolic Differentiation of Alzheimer’s Disease in Mice Across Three Brain Regions to Explore Changes in Response to Anesthesia in Surgery

Motivation: Use MRS-based metabolomics to differentiate brain regions between wildtype and 'early-stage' AD (3-4mo) mice, creating a baseline molecular profile to assess changes in response to AD-promoting stimuli. Goal(s): Identify metabolomic differences in: frontal cortex, dorsal hippocampus (DHP) and ventral hippocampus (VHP). Approach: Ex vivo 5xFAD mice brain tissues were analyzed using 1H HRMAS-MRS. Machine learning and statistical analysis of 5 neurochemicals and ~17 data points/group was performed. Results: The largest separation was between the cortex and VHP. NAA, aspartate and glutamate were higher in the cortex than VHP, GABA was similar in both, and scyllo-inositol was higher in VHP. Impact: HRMAS-MRS, machine learning and 5 neurochemical metabolites differentiated the dorsal hippocampus, ventral hippocampus and frontal cortex, with the largest separation between the latter two. This created a baseline metabolomic profile to probe the impact of anesthesia as an AD-promoting stimulus.