MAPT and early-onset autosomal dominant Alzheimer disease: This backdrop includes Alzheimer’s disease model system data which support a neuroprotective role for IGFs, and a hypothesis that resistance to this signaling may lead to disinhibition of pro-apoptotic and pro-inflammatory pathways as well as tau phosphorylation related to phosphatidylinositol 3-kinase, protein kinase B (Akt) and glycogen synthase kinase 3 pathways (Benarroch, 2012).