Abstract
Studies of the tau protein and its pathological fate as a neurofibrillary tangle have been a pillar of Alzheimer's disease research. The understanding of the fundamental position that tau occupies in the disease cascade is a tribute to an international group of scientists who brought rigor, candid assessments of data, and critical thinking to the problem. The tau pathway winds its way from astute clinical observations to pathological correlations, from molecular and cellular experiments to mining informatic data, and from animal behavior to the biophysics of protein structure. For most the vindication of this tireless effort will come from tau-based therapies; but for others the remarkable biology revealed by the Alzheimer disease process has been its own reward.