We performed a large-scale, intact glycopeptide-based glycoproteomics study of human brain tissue samples from neuropathologically confirmed AD cases and their age-matched controls. The study provided a system-level view of human brain protein glycoforms and site-specific glycan modifications. Our analyses revealed previously unknown changes in protein glycoforms and site-specific glycans in AD brain. Our findings provide novel insights into the roles of glycan modifications in brain dysfunction in AD.