. In this study, we have investigated the capacities of last-generation Ultra-High Resolution Q-Tof systems to deal with high complexity intact protein samples, have developed the tools to process the intact protein data in an existing label-free quantification pipeline, and have evaluated the approach on a cohort of patients suffering from neurodegenerative disease in a proof-of concept study. Several proteoforms have been pointed out for their capacity to distinguish Alzheimer disease patients from patients suffering from other neurodegenerative disease and have been characterized.