 This interaction decreases APP endocytosis leading to an increase in amyloid-β production.In addition, the expression of ApoER2 within intracellular compartments leads to increased gamma secretase activity, a protease which works to cleave APP into Aβ.ApoER2 splice variants can act as a receptor for alpha-2-macroglobulin which can have a role in clearance of alpha-2-macroglobulin/proteinase complex.