Here, we describe 12 phosphomimetic serine/threonine-to-aspartate mutations in tau, which we term PAD12, that collectively induce the in vitro assembly of full-length three-repeat tau into filaments with the same structure as paired helical filaments extracted from the brains of individuals with Alzheimer's disease. The gene discussed is MAPT; the disease is early-onset autosomal dominant Alzheimer disease.