Proteomic analysis of 5xFAD/Mdk-KO mouse brain reveals proteome-wide changes. This study investigates the impact of midkine (MDK) knockout in 5xFAD mouse model using comprehensive mass spectrometry-based whole proteome profiling. The data demonstrates significant alterations in amyloid formation and microglial activation, providing insights into MDK's protective role in Alzheimer's disease pathology.