The quantitative proteomics analysis of brain tissue lysates from APP/PS1 Tg mice and APP/PS1 Tg/sEH−∕− mice revealed that several significant pathways and cellular processes, including translational regulation, oxidative stress, and cytoskeleton reorganization, are possibly associated with the function of sEH as well as the pathogenesis of AD. Here, EPHX2 is linked to Alzheimer disease.