Abstract

Tackling microtubule-tau interactions Alzheimer's disease is a major cause of death in the elderly. Disease progression is associated with the accumulation of neurofibrillary tangles composed of tau, a protein important for neuronal development and function. Tangle formation is preceded by phosphorylation events that cause tau to dissociate from its native binding partner, microtubules. Microtubule-tau interactions have been mysterious. Kellogg et al. used cryo–electron microscopy and molecular modeling to show how tau interacts with the outer surface of the microtubule, stapling together tubulin subunits and thus stabilizing the polymer. A key tau amino acid within the tightly bound segment between tubulin subunits corresponds to a clinically relevant site of tau phosphorylation, explaining the competition between microtubule interaction and tau aggregation. Science , this issue p. 1242