Updated project metadata. This study has investigated several parameters to obtain increased detection of the amyloid plaque intact protein profile, including a comparison of commonly used MALDI matrices, acid based reduction of signal suppression as well as the combination of strong acid based protein aggregate extraction from laser microdissection plaques to increase detection of proteoforms. Female APPPS1-21 transgenic mice were analyzed by MALDI Imaging with different matrices on a Ultraflextreme MALDI TOF/TOF instrument followed by data analysis in SCiLS Lab software. A combination of formic acid treatment of laser capture microdissected plaques was further utilized to expand the analysis and validation of amyloid plaques.