Tau monomer from aggregate-containing cell models and tauopathy brains adopts discrete structures that act as templates, dictating the conformation of distinct strains that result from its seeding activity.
A novel regulatory cascade downstream of Tau and spectraplakins ensures that synaptic proteins are delivered to axonal terminals in the developing and ageing brain, providing potential explanations for precocious synapse loss in dementias.
Liquid-liquid phase separation of tau is demonstrated to be an equilibrium state, stable only within a narrow range near physiological conditions, and thus has the capacity to regulate biological processes.
Cryo-EM structures of heparin-induced tau filaments differ from those observed in neurodegenerative disease, illustrating their structural versatility, and prompting questions about the relevance of in vitro amyloid models.
Tau protein exists as two conformational ensembles, one inert, and another that has intrinsic properties of self-association, triggers seeding in cells and in vitro, and is associated with Alzheimer's disease.
Aβ inhibitors effectively block its aggregation, while also reducing seeding of tau aggregation from Aβ, tau, and AD derived fibrils, suggesting the two share a structurally related disease relevant interface.