IGF1 and Alzheimer disease: Also, the activation of PI3K by insulin and IGF-1 is markedly disturbed in Alzheimer Disease (AD) brain, leading to sustained activation of Akt (Pei et al., 2003; Rickle et al., 2004), which in turns causes neurons to become increasingly and ultimately totally resistant to both agonists (Moloney et al., 2010; O'Neill et al., 2012; Talbot et al., 2012).