INS and Alzheimer disease: Studies have shown AD progression is linked to dysregulated insulin signaling in the frontal cortex and hippocampus, and postmortem analysis of human hippocampal tissue shows correlation between high serine-inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) and those of oligomeric Aβ plaques, which were negatively associated with working memory and episodic memory [5].