Phase separation of the microtubule-associated protein tau

Abstract The aggregation and misfolding of the neuronal microtubule-associated protein tau is closely linked to the pathology of Alzheimer’s disease and several other neurodegenerative diseases. Recent evidence suggest that tau undergoes liquid–liquid phase separation in vitro and forms or associates with membrane-less organelles in cells. Biomolecular condensation driven by phase separation can influence the biological activities of tau including its ability to polymerize tubulin into microtubules. In addition, the high concentrations that tau can reach in biomolecular condensates provide a mechanism to promote its aggregation and the formation of amyloid fibrils potentially contributing to the pathology of different tauopathies. Here, the authors discuss the role of tau phase separation in physiology and disease.