The molecular mechanisms underlying AD pathogenesis are still not fully understood. Lipids have been implicated to play a central role in AD pathogenesis. Indeed, a global alteration is observed in cerebrospinal fluid, blood, and brain tissue extracts from AD patients before . Multiple studies have also demonstrated alterations of various lipids and lipid metabolites both between Aβ plaque microenvironment, and even within single Aβ plaques ). Here, mass spectrometry imaging (MSI) has been demonstrated to be valuable for precise characterization of chemical microenvironments of plaques including both plaque pathology associated lipids and peptides.