We also found that levels of clathrin heavy and light chains were similarly reduced in these lines, compared to AD1. An average of 40% reduction was observed in subjects AD3, AD4 and AD5, with insignificant reduction found in subject AD2. Clathrin and its partner Adaptor Protein 2 are involved in endocytosis of APP and its C-terminal fragments [38, 39]. A reduction of clathrin and related proteins likely decreased the level of APP to interact with BACE1 and subsequent cleavage for Aβ production. When the BACE1 inhibitor was present, its efficacy was more obvious in those lines compared to AD1 (Fig 9B).
