Microtubule-associated protein tau oligomer (oTau)

Microtubule-associated protein tau (MAPT) is a critical protein that stabilizes neuronal microtubules, facilitating axonal transport and maintaining structural integrity (UniProt P10636). In tauopathies like Alzheimer's disease, tau undergoes abnormal post-translational modifications, such as hyperphosphorylation, which causes it to dissociate from microtubules and form soluble, high-molecular-weight (HMW) oligomers (PubMed: 26466027). These oligomeric species are increasingly recognized as the primary neurotoxic forms of tau, capable of propagating between neurons in a prion-like manner and inducing synaptic dysfunction and cell death (PubMed: 31515450). Therapeutic strategies targeting tau oligomers include monoclonal antibodies designed to neutralize extracellular species and prevent 'seeding,' as well as small molecules aimed at inhibiting the aggregation process (PubMed: 32814900). Current clinical research focuses on identifying specific epitopes within the microtubule-binding region (MTBR) or N-terminus that are exposed in pathogenic oligomers to allow for selective targeting without affecting healthy monomeric tau (ClinicalTrials.gov).

Other names

High-molecular-weight tauHMW tauPathogenic tau oligomerSoluble tau aggregateTau protofibrilTau species

Monoclonal antibodies and small molecules target tau oligomers to inhibit their formation, neutralize extracellular species to prevent cell-to-cell spreading (seeding), and promote the clearance of toxic aggregates through microglial phagocytosis or proteasomal degradation (PubMed: 32814900, PubMed: 31515450).