In a TMT labeled MS2-based quantitative proteomic study, researchers found that succinylation of multiple mitochondrial proteins declined, and succinylation of small number of cytosolic proteins increased.173 The largest increases occurred at critical sites of amyloid precursor protein (APP) (K612) and microtubule-associated tau (K311), which are crucial to AD progression.174–177 Mechanistically, succinylation of APP disrupted its normal proteolytic processing thereby promoting Aβ accumulation and plaque formation. This evidence concerns the gene APP and Alzheimer disease.