Microtubule-associated protein tau (phosphorylated at Serine 422) (pS422-Tau)

Microtubule-associated protein tau (MAPT) is a protein primarily expressed in neurons that functions to stabilize microtubules and support axonal transport (UniProt P10636). In neurodegenerative conditions known as tauopathies, tau becomes hyperphosphorylated, leading to its detachment from microtubules and the formation of neurotoxic aggregates (PubMed: 32839610). Phosphorylation at the Serine 422 (S422) residue is a pathological hallmark that appears early in the disease progression of Alzheimer's disease and other tauopathies (PubMed: 25561413). This specific modification is associated with the transition of tau from a soluble state to insoluble filaments and is considered a key driver of tau-mediated neurotoxicity and spreading (PubMed: 29453111). Because pS422 is largely absent in healthy brains, it serves as a highly specific therapeutic target for immunotherapy. Current drug development efforts, such as the vaccine ACI-35.030 and the monoclonal antibody Lu AF87908, aim to selectively bind and clear pS422-Tau species to prevent the propagation of tau pathology (ClinicalTrials.gov: NCT04445831, NCT04149860). These interventions are designed to halt cognitive decline by reducing the burden of pathological tau while sparing the functional, non-phosphorylated protein.

Other names

MAPTPhospho-tau (Ser422)pTau422Ser422-phosphorylated tauTau-pS422

Passive and active immunization to facilitate the clearance of pathological tau aggregates and inhibit the trans-synaptic spread of tau pathology.