Tau aggregate (Tau aggregates)

Tau aggregates refer to insoluble, misfolded assemblies of tau protein that form within neurons and glial cells. Normally, tau is a microtubule-associated protein critical for stabilizing the microtubule cytoskeleton and supporting axonal transport in neurons. In disease states—most notably Alzheimer's disease and other tauopathies—tau undergoes abnormal post-translational modifications, especially hyperphosphorylation, leading to its dissociation from microtubules and aggregation into paired helical filaments, straight filaments, and various types of neurofibrillary tangles. These aggregates disrupt cellular function, impair synaptic signaling, and ultimately drive neurodegeneration. Tau aggregates differ in structure and location among disease subtypes, and recent cryo-EM studies have classified tauopathies by distinct filament folds. Therapeutic approaches include preventing tau aggregation, promoting its clearance, and inhibiting toxic post-translational modifications. Tau aggregate load—detected by CSF biomarkers and imaging—is a key prognosis and patient selection marker in clinical research. Despite being a central target, clinical translation has been hampered by difficulties in targeting abnormal tau without affecting its essential physiological function.

Other names

Neurofibrillary tanglesTau fibrilsHyperphosphorylated tau aggregatesPaired helical filaments (PHFs)Straight filaments (SFs)Pathological tau assembliesMAPT aggregates

Inhibition of tau-tau aggregation Stabilization of tau protein in non-aggregated states Promotion of tau clearance (immunotherapeutics) Blockage of filament formation (steric zipper inhibitors, small molecules) Modulation of tau phosphorylation and post-translational modification