Microtubule-associated protein tau (hyperphosphorylated) (Tau (hyperphosphorylated) or p-Tau)

Hyperphosphorylated tau is a pathologically modified form of the microtubule-associated protein tau, which in the central nervous system is normally responsible for stabilizing microtubules and supporting axonal transport[5][1][3]. In Alzheimer’s disease and related tauopathies, tau becomes abnormally hyperphosphorylated at multiple serine and threonine residues, primarily by the action of proline-directed kinases such as GSK3β and CDK5[4][6][7]. This hyperphosphorylation reduces tau’s affinity for microtubules, leading to their destabilization, and promotes pathological aggregation of tau into paired helical filaments and neurofibrillary tangles, which are hallmarks of Alzheimer’s pathology[5][7][1]. Hyperphosphorylated tau is considered a major driver of neurodegeneration and cognitive decline, as its accumulation is closely correlated with disease severity[7][9]. Therapeutic strategies aim to target kinases responsible for tau phosphorylation, activate phosphatases for removal of phosphate groups, or neutralize toxic p-Tau with antibodies or vaccines[2][4][6][9]. Despite significant interest, clinical efficacy and safety of these approaches remain areas of active research, and modulation of p-Tau for therapy is a complex challenge due to tau’s essential physiological functions and diverse post-translational modifications[6][9][4][2].

Other names

Hyperphosphorylated taup-TauPathological tauPHF-tau (paired helical filament tau)Neurofibrillary tangle tauA68 (older literature)

Inhibition of tau kinases (e.g., GSK3β, CDK5, ERK2); Activation of protein phosphatases (e.g., PP2A); Immunotherapy against pathological p-Tau species (antibodies and vaccines targeting specific phosphorylated epitopes); Prevention of tau aggregation/seeding