Liquid-liquid phase separation of tau in Alzheimer's disease.

Liquid-liquid phase-separated tau colocalizes with and stabilizes Aβ oligomers

It is demonstrated that tau condensates act as reservoirs for Aβ oligomers under liquid-liquid phase separation conditions, with Aβ oligomers reducing tau dynamics, potentially providing a conducive environment for Aβ oligomer clustering.

Osmolytes suppress liquid‒liquid phase separation and the aggregation of Tau.

Tau liquid-liquid phase separation (LLPS) is increasingly recognized as an early event that promotes pathological aggregation in Alzheimer's disease and other tauopathies. Osmolytes are natural chemical chaperones that stabilize protein conformations, yet their effects on Tau phase behavior remain poorly understood. He...

Cofactor-Free Tau Filaments Are Dynamic and Undergo Structural Evolution Driven by Thermodynamic Control

Environmental factors, such as mechanical stress and/or polyanions, play an important role in promoting the thermodynamic stability of otherwise dynamic tau fibrils, and it is speculated that, in patients, such factors might contribute to the maturation of disease-specific conformers.

Charge-driven remodelling of monomeric Tau determines its phase behaviour

Tau transitions from a functional microtubule-stabilising monomer into pathological aggregates in tauopathies. However, the molecular mechanism by which soluble Tau transitions into insoluble aggregates remains poorly understood. Here, we show that modulation of Tau’s internal charge-charge interactions by pH and ionic...

From dynamic condensates to pathological assemblies: the phase behavior of tau and α-synuclein

Neurons rely on precise protein folding, trafficking, and turnover to maintain synaptic function. Disruption of proteostasis promotes misfolded proteins that impair axonal transport, mitochondrial function, and signalling, contributing to neuronal loss. Although neurodegeneration has traditionally focused on stable amy...

Neuronal lipid composition regulates distinct states of full-length tau assembly, mechanics and membrane interactions