MAPT and Alzheimer disease: Though the gene encoding tau is not genetically linked to AD, mutations in MAPT cause FTDP-17 [29,30], and missense mutations have also been found in progressive supranuclear palsy [31], corticobasal degeneration [32,33] and in conditions that closely resemble Pick's disease [34,35], thus providing evidence that disrupting tau homeostasis suffices to cause neurodegeneration (Fig. 1).