IRS1 and Alzheimer disease: This observations were subsequently corroborated by studies demonstrating progressively increased phosphorylation of IRS-1 in inhibitory serine residues, accompanied by augmented levels of their activated serine-kinases GSK-3, IKK, JNK, mTOR, and PKCζ/λ, as patients evolve from non-demented to MCI to AD (Bomfim et al., 2012; Talbot et al., 2012).