IRS1 and Insulin resistance: The first step in the insulin pathway activation, the receptor autophosphorylation, is followed by the Tyr phosphorylation of IRS1; however, in AD brains many groups reported increases in p(Ser)-IRS1, a marker of insulin resistance, instead of p(Tyr)-IRS1 (Steen et al., 2005; Moloney et al., 2010; Bomfim et al., 2012; Talbot et al., 2012; Figure 1).