Updated project metadata. We performed a systems-level study of disease-associated proteome changes in human frontal cortex of Alzheimer’s disease (AD) patients using an integrated approach that combines mass spectrometry-based quantitative proteomics, differential expression analysis, and co-expression network analysis. Our analyses of 16 human brain tissues from AD patients and age-matched controls showed organization of the cortical proteome into a network of 24 biologically meaningful modules of co-expressed proteins. Of these, 5 modules are positively correlated to AD phenotypes with hub proteins that are up-regulated in AD, and 6 modules are negatively correlated to AD phenotypes with hub proteins that are down-regulated in AD.