IRS2 and Alzheimer disease: In contrast to this observation, Freude et al. [52] showed that impaired IGF-1/insulin receptor substrate 2 (IRS-2) signaling prevented premature death and delayed amyloid accumulation predominantly in the hippocampus in mice with Swedish mutation of amyloid precursor protein (APP) as a model of AD and deficient for IRS-2, neuronal IGF-1 receptor or neuronal insulin receptor.