Abstract #3949

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

Rajshree Ghosh Biswas¹, Zeynep M Suar¹, Christina Tognoni^2,3, Isabel Carreras^2,3, Alpaslan Dedeoglu^2,3, Yiying Zhang⁴, Zhongcong Xie⁴, Leo Cheng⁵, and Bruce Jenkins¹

¹Radiology, Massachusetts General Hospital, Charlestown, MA, United States, ²Neurology, Boston University, Boston, MA, United States, ³Boston Veterans Affairs Medical Center, Boston, MA, United States, ⁴Anesthesia, Massachusetts General Hospital, Boston, MA, United States, ⁵Harvard T.H. Chan School of Public Health, Boston, MA, United States

Synopsis

Keywords: Alzheimer's Disease, Alzheimer's Disease, Anesthesia, post-operative delirium

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.

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