To reveal the pathologic mechanisms involved in large deposits of Aβ amyloid plaques selectively in subiculum region during early stage of AD pathogenesis, high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to profile the proteomic changes in different stages of AD. We analyzed the proteome of SUB regions microdissected from wild type (WT) and 5×FAD (AD) mice at 3, 6 and 12 months of age with three biological replicates via data-independent acquisition (DIA) proteomic approach, which had higher stability and coverage and less missing data than label-free quantitative method (LFQ) facilitating identification of low-abundance proteins [1]. In-depth analysis of all replicates using Spectronaut identified 131483 peptides assembling into 8948 protein groups, and more than 4000 proteins was detected in each SUB region, of which 4840 proteins were quantified.