Updated project metadata. Amyloid plaques (Aβ plaques) are one of the hallmarks of Alzheimer’s disease (AD). The main constituent of Aβ plaques is beta-amyloid peptides but a complex interplay of other infiltrating proteins also co-localizes. We focused on proteomic differences between Aβ plaques and adjacent control tissue in the transgenic mouse model of AD (APPPS1-21) and in similar regions from non-transgenic littermates. A microproteomic strategy included isolation of regions of interest by laser capture microdissection and analyzed by label-free liquid chromatography mass spectrometry. An in-solution digest protocol with a buffer containing an acid-labile surfactant was used to increase protein solubilization and protease efficiency.