This study identified key biochemical pathways and protein changes in the Alzheimer's disease (AD) human hippocampus, revealing increased expression of proteins VGF, GFAP, HSPB1, and APP, with UBC being most centrally involved, and highlighted the roles of four hub proteins (CD44, APP, ITGB2, APOE) linked to amyloid plaques and two (RPL24, RPS23) to neurofibrillary tangles, along with the impact of modified proteins on immune activation and synaptic disruption, uncovering potential therapeutic targets involving specific proteins, microRNAs, and transcription factors.