<h4>Introduction</h4>The locus coeruleus (LC) is an early site of Alzheimer's disease (AD) pathology, yet the role of brainstem astrocytes in early, sex-dependent vulnerability remains unclear.<h4>Methods</h4>In 2- to 3-month-old APP/PS1 mice, we combined in vivo proton magnetic resonance spectroscopy (MRS) of the brainstem with region-resolved molecular analyses, including quantitative real-time polymerase chain reaction, amyloid beta 42 (Aβ42) oligomers enzyme-linked immunosorbent assay, lactate assay, immunohistochemistry, immunoblotting, astrocyte isolation, and 3D structural assessment. This evidence concerns the gene APP and early-onset autosomal dominant Alzheimer disease.