On a cellular basis, inhibition of insulin/IGF signaling contributes to AD-type neurodegeneration by increasing: 1) the activity of kinases that aberrantly phosphorylate tau; 2) expression of AβPP and accumulation of AβPP-Aβ; 3) levels of oxidative and endoplasmic reticulum (ER) stress; 4) the generation of reactive oxygen and reactive nitrogen species that damage proteins, RNA, DNA, and lipids; 5) mitochondrial dysfunction; and 6) activation of pro-inflammatory and pro-death cascades. Here, MAPT is linked to Alzheimer disease.