INS and hyperinsulinism: For Aβ aggregation, hyperinsulinemia results in the downregulation of insulin receptors with consequent alteration in insulin signaling in the brain, which in turn elevates the generation of Aβ and decreases its clearance by hampering the production of the enzyme required for its degradation, IDE, as well as competing with Aβ for it (Zhao et al., 2004; Luchsinger, 2008).