Understanding the progression of Alzheimer’s Disease in 5XFAD transgenic female mice using 1H‐[13C]‐NMR Spectroscopy

Abstract

AbstractBackground5XFAD female mice have been reported to exhibit severe plaque loading at an early age. However, brain glucose metabolism is poorly understood in this model. The objective of the current study was to understand neurometabolism and its role in disease progression and pathophysiology in female transgenic mice at various age points.MethodThe current study uses a tracer‐based approach, which involves infusion of [1,6]13C2 labeled glucose into AD mouse model 5XFAD, to observe the changes in the neuronal glucose oxidation in this pathological condition with the progression of age.ResultThere was a significant memory loss in the 6 months‐old (6M) transgenic females compared to the 15 months‐old (15M) animals through Novel Object Recognition and Y‐Maze tests. The neurochemical profile showed higher myo‐inositol levels in the cerebral cortex in the 15M mice wrt. the 6M ones, which implies that there is increased gliosis and neuroinflammation in the former. There is also an increased level of glutamine in the 15M mice, which is known to act as an osmolyte and cause brain edema. However, the cerebral metabolic rates of glucose oxidation in Glutamatergic and GABAergic neurons did not show a significant difference in 5xFAD female mice when compared with wild‐type mice of the same age.ConclusionThe imperturbation in the female mice might be linked to some active underlying neuroprotective mechanism and needs to be explored further. Also, to get a clear picture of the gender‐dependent AD progression, studies need to be conducted in the age‐matched male mice as well.