• Prevention of in vitro microtubule assembly (65) and depolymerization (66, 67) by p-tau isolated from human AD brain tissue. • Reduced microtubule density and axonal degeneration in neuronal cultures (68, 69), in Tg mice expressing h-tau (70) or PS19 tau (71), and in AD patients (72). • Contribution of tau-dependent loss of microtubule stability to cognitive deficits in tau 3xTg and rTg4510 mouse models (73). • Tau-related microtubule destabilization is accompanied by Aβ-induced neurodegeneration (74–77). Here, MAPT is linked to Alzheimer disease.