In this study, matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI–MSI)‐based spatial metabolomics and liquid chromatography‐mass spectrometry (LC–MS)‐based metabolomics were applied to explore the anti‐AD effect of PRE via improving the system‐wide metabolic disorders in APPswe/PSEN1dE9 (APP/PS1) double transgenic AD model mice. Here, APP is linked to Alzheimer disease.