The pleiotropic pathogenesis of Alzheimer’s disease (AD), along with drugs developed in the “inside-out approach,” which relied heavily around halting/clearing intracellular aggregates of the hyper phosphorylated tau protein and extracellular plaques of the β-amyloid (Aβ) peptide, led to the failure of most clinical trials despite decades of research. Here, MAPT is linked to Alzheimer disease.