Sex Specific changes in Glutamate and Other Neurometabolites in a Mouse Model of Alzheimer’s Disease: A GluCEST MRI and 1H-MRS Study

Motivation: It is well known that prevalence and progression of Alzheimer’s disease (AD), is different across two sexes. Glutamate regulates various cognitive functions including learning and memory and is known to be perturbed in AD though sex specific in vivo studies are limited. Goal(s): To monitor sex-specific changes in cerebral glutamate and other neurometabolites in APPNL-F/NL-F and WT mice. Approach: Glutamate weighted Chemical Exchange Saturation Transfer (GluCEST) MRI and localized 1H-MRS. Results: Significant neurometabolite alterations in the hippocampus of male AD mice were observed, while females remained unaffected. This could be broadly attributed to neuroprotective effects of female reproductive hormones e.g., estrogen. Impact: Although the sex bias in AD pathology has been long known, the actual mechanism remains elusive. Results obtained from this study provides a way to further explore the factors responsible for intact regional glutamate levels in female AD mice.