Alzheimer’s disease (AD) is characterized by the accumulation of pathological amyloid aggregates, yet methods for spatially resolved, proteome-wide profiling of amyloid composition and their microenvironment remain limited. Here, we report Eosin Y (EY) as an easily accessible and efficient organic photocatalyst for pan-amyloid binding, labeling, and proteomic profiling in AD brain tissues. EY demonstrated strong binding affinity toward various amyloids. Upon green-light irradiation in the presence of aryl azide, EY enabled rapid and covalent labeling of amyloid structures and this process was demonstrated to be a single-electron transfer (SET) pathway. Application of this strategy to 5×FAD mouse brain tissue enabled successful enrichment and proteomic identification of key AD related proteins, including App, Apoe, and Gfap. Together, this work demonstrates a microscopy free method for the molecular dissection of amyloid plaques, advancing the toolbox for neurodegenerative disease research