Updated project metadata. Protein aggregation of amyloid-β (Aβ) peptides and tau are pathological hallmarks of Alzheimer's disease (AD), which are often resistant to detergent extraction and thus enriched in the insoluble proteome. However, additional proteins that co-accumulate in the detergent-insoluble AD brain proteome remain less studied. Here we comprehensively characterized key proteins and pathways in the detergent-insoluble proteome from human AD brain samples by differential extraction, coupled with tandem mass tags labeling and two-dimensional liquid chromatography tandem mass spectrometry (TMT-LC/LC-MS/MS).