The evidence that GSK3 plays a central role in AD and that its deregulation accounts for many of the pathological hallmarks of the disease in both sporadic and familial AD cases, has led us to formulate the ‘GSK3 hypothesis of AD.’ Evidence from our group and others suggests that GSK3 is intimately involved in the hyper-phosphorylation of tau, memory impairment, the increased production of Aβ and in inflammatory responses (Fig. 1). The gene discussed is MAPT; the disease is Alzheimer disease.