Impaired insulin transduction with reduced insulin and IGF-1 receptors (IR and IGF-1R, respectively); insulin and IGF-1 mRNA expression and protein concentrations; and downstream signaling elements, such as insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), were observed in the brains of AD patients (156). Here, IRS1 is linked to Alzheimer disease.