Microtubule-associated protein tau (MAPT) (residues 2-18) (Tau 2-18)

The microtubule-associated protein tau (MAPT) N-terminal region, specifically residues 2-18, is a critical pathological epitope involved in the progression of Alzheimer's disease and other tauopathies (UniProt P10636). In its physiological state, tau is an intrinsically disordered protein that stabilizes microtubules and regulates axonal transport within neurons. However, in disease states, tau undergoes conformational changes and hyperphosphorylation that expose the N-terminal "phosphatase-activating domain" (PAD), which includes the 2-18 sequence (Kolarova et al., 2012). This exposure is linked to the disruption of fast axonal transport and the formation of neurotoxic aggregates that spread throughout the brain. Therapeutic agents like ontamalimab (E2814) are designed to bind this specific epitope to neutralize extracellular tau "seeds" and prevent the trans-cellular propagation of pathology (Roberts et al., 2020). By targeting this region, these therapies aim to reduce the accumulation of neurofibrillary tangles and slow cognitive decline in patients (Eisai Co., Ltd., 2021). This approach specifically targets the spreading mechanism of tau, which is closely correlated with clinical symptoms in Alzheimer's disease.

Other names

N-terminal tau epitopeTau N-terminusTau 2-18 regionPhosphatase-activating domain (PAD) fragmentMAPT 2-18

Passive immunotherapy involving the binding of monoclonal antibodies to the N-terminal 2-18 amino acid sequence of tau to neutralize extracellular tau seeds and prevent their propagation between neurons (Roberts et al., 2020).