Microtubule-associated protein tau (MAPT) phosphorylated at Ser396 and Ser404 (pTau396/404)

Microtubule-associated protein tau (MAPT) is a primary component of the neuronal cytoskeleton, where it functions to stabilize microtubules and facilitate axonal transport (Source: UniProt P10636). In pathological states such as Alzheimer's disease and other tauopathies, tau undergoes hyperphosphorylation at specific residues, including the Ser396 and Ser404 sites within the C-terminal 393–408 region (Source: Mondragón-Rodríguez et al., 2014). This modification leads to the detachment of tau from microtubules and its subsequent aggregation into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). These aggregated, phosphorylated forms are considered major drivers of neurodegeneration and correlate strongly with the progression of cognitive decline (Source: Gozes, 2010). Therapeutic interventions targeting pTau396/404 and PHF-tau, such as monoclonal antibodies and vaccines, aim to neutralize and clear these toxic species to prevent the trans-synaptic spread of tau pathology (Source: AC Immune, 2023). By reducing the burden of these pathological species, these treatments seek to preserve neuronal function and slow clinical decline.

Other names

Phospho-tau (Ser396/Ser404)PHF-tauPaired helical filament taupS396/pS404 tauHyperphosphorylated tauTau 393-408 epitope

Active and passive immunotherapy targeting specific phospho-epitopes and aggregated tau species to promote clearance and prevent pathological spreading (Source: AC Immune, 2023; Lilly, 2021).