Given the remarkable convergence of the key AD-related entities currently under investigation on the regulation of Aβ levels, notwithstanding the exception of tau which has a fundamentally different relationship with Aβ, it may be timely to review some of the major candidate mechanisms via which it could exert its pathological effects at the synapse, before briefly describing new findings that may help to address one of the weaknesses of the amyloid hypothesis, the absence of a mechanism for the downstream recruitment of tau. The gene discussed is MAPT; the disease is Alzheimer disease.