Microtubule-associated protein tau, hyperphosphorylated form (tau (hyperphosphorylated), pTau)

Hyperphosphorylated tau protein is a pathological form of the microtubule-associated protein tau that has undergone excessive phosphorylation at multiple serine, threonine, and sometimes tyrosine residues. Under normal physiological conditions, tau stabilizes microtubules in neurons, supporting axonal integrity and transport. In Alzheimer's disease and related neurodegenerative disorders (tauopathies), tau becomes abnormally hyperphosphorylated, reducing its affinity for microtubules and promoting its self-assembly into insoluble aggregates called paired helical filaments and neurofibrillary tangles. These aggregates disrupt neuronal structure, interfere with synaptic and nuclear functions, impair axonal transport, and ultimately contribute to neurodegeneration and cognitive decline[3][4][5][6][7]. Hyperphosphorylated tau is both a hallmark and a therapeutic target in Alzheimer’s disease, frontotemporal dementia, and many other neurodegenerative conditions[5][6][10]. Modulation of tau phosphorylation or inhibition of its aggregation are major drug discovery approaches, and hyperphosphorylated tau species (especially pTau181 and pTau217) are important biomarkers for both diagnosis and monitoring of therapeutic efficacy[6][5]. Hyperphosphorylated tau is not a physiological gene product, but rather a disease-relevant post-translationally modified and aggregated species of tau protein.

Other names

Tau protein (hyperphosphorylated)pTauhyperphosphorylated MAPTpaired helical filament taupathological tau

Inhibition of tau aggregation (tau aggregation inhibitors); Immunotherapy targeting extracellular or aggregated tau (anti-tau antibodies); Inhibition of tau hyperphosphorylation (kinase inhibitors, O-GlcNAcase inhibitors); Enhancement of tau clearance (antibody-mediated phagocytosis, autophagy activators)