Microtubule-associated protein tau (phosphorylated at Threonine 181) (p-tau181)

Phosphorylated tau protein at threonine 181 (p-tau181) is a pathological isoform of the microtubule-associated protein tau, which normally plays a critical role in stabilizing neuronal microtubules and maintaining axonal transport [8, 14]. In Alzheimer's disease (AD) and other tauopathies, tau undergoes hyperphosphorylation at specific sites, including threonine 181, leading to its dissociation from microtubules and the formation of neurotoxic aggregates known as neurofibrillary tangles [3, 14]. This pathological process is strongly associated with synaptic dysfunction and the progression of cognitive decline [7, 15]. p-tau181 has emerged as a highly sensitive and specific biomarker in both cerebrospinal fluid and plasma, allowing for the early detection of AD pathology and the monitoring of disease progression [11, 12, 16]. Therapeutic strategies targeting p-tau181 include active vaccines like ACI-35.030 and passive immunotherapies that aim to clear phosphorylated tau species from the brain [1, 6]. Other approaches involve the use of kinase inhibitors, such as tideglusib, to prevent tau hyperphosphorylation, and experimental chimeras like DEPTACs that promote the dephosphorylation of the protein to restore its physiological function [3, 4, 10].

Other names

Phospho-tau (Thr181)p-T181MAPT (pT181)Phosphorylated tau-181Tau phosphorylated at threonine 181

Active and passive immunotherapy, kinase inhibition, microtubule stabilization, and targeted dephosphorylation via chimeric molecules.