MR Spectroscopy Detects Sex-Specific Early Brainstem Glial Activation in a Mouse Model of Alzheimer’s Disease

Motivation: Identifying pre-diagnostic biomarkers is crucial in the context of Alzheimer's disease (AD). Goal(s): We aimed to assess the predictive capability of magnetic resonance spectroscopy (MRS) in identifying early stages of AD. Approach: MRS was conducted on the brainstem of both male and female APP/PS1 mice, with the results validated histopathologically and further corroborated through behavioral experiments. Results: MRS revealed altered astrocyte metabolism in the brainstem of female APP/PS1 mice, but not in males. Our findings highlight the predictive potential of brainstem MRS as an early biomarker for detecting sex-specific onset of pathological changes in AD. Impact: Including brainstem MRS results in routine clinical evaluations could allow clinicians to offer tailored lifestyle advice or enroll individuals in prevention trials focused on maintaining brain health.