INS and Alzheimer disease: Future multi-modal therapies for AD should be directed at multiple levels of demonstrated weakness within the insulin/IGF signaling cascade, beginning with receptor sensitizers, agents to promote insulin production and release, e.g. GLP-1, inhibitors of oxidative stress, radical formation, and metal ion accumulation, tau phosphorylating kinase modulators, and co-factors that support glucose utilization, mitochondrial function, and energy metabolism.