mutation at the BACE1 cleavage site [40], increases the expression levels of several genes like APP and BACE1. High expression of substrate and enzymatic activity may compensate for the reduction by BACE1 inhibitors. Similarly, levels of clathrin proteins were higher in neurons from AD1 subject (Table 2), indicating a better endocytic process for APP and its cleavage by BACE1 for Aβ generation. Our MS-based proteomic analysis of all 3D neuronal culture provides many proteins that were up/down-regulated across five lines, presenting a venue to understand the individual profile of drug pharmacology using systems biology.
