MAPT and early-onset autosomal dominant Alzheimer disease: Multiple open questions remain: the structural features of Tau in the tau:tubulin co-polymer, the molecular definition of toxicity, the mechanism of action of small molecules that interfere with the Tau oligomer or fiber formation, and how do phosphorylation and other PTMs regulate these aspects, etc. We hope that the technique will contribute productively to the goal of understanding, at the molecular level, the regulation of Tau’s (dys) function, and ultimately help to find disease-modifying agents for Alzheimer’s disease and related Tauopathies.