Phosphorylated tau protein at threonine 217 (p-tau217)

Phosphorylated tau protein at threonine 217 (p-tau217) is a specific pathological isoform of the microtubule-associated protein tau, characterized by the addition of a phosphate group at the threonine residue at position 217. In a healthy state, tau stabilizes microtubules and supports axonal transport; however, hyperphosphorylation at sites like T217 causes tau to detach from microtubules, leading to cytoskeletal instability and the formation of neurotoxic neurofibrillary tangles. p-tau217 has gained significant prominence as a highly sensitive and specific blood-based biomarker for Alzheimer's disease, with levels rising in the brain and periphery up to two decades before the onset of clinical symptoms. It is strongly correlated with amyloid-beta plaque accumulation and is used to differentiate Alzheimer's from other tauopathies and dementias. In the context of drug development, p-tau217 serves as a critical pharmacodynamic endpoint for evaluating the efficacy of disease-modifying therapies, including anti-amyloid antibodies and tau-targeted agents such as antisense oligonucleotides and small-molecule kinase inhibitors.

Other names

pTau217Phospho-tau (Thr217)taupT217Phosphorylated microtubule-associated protein tau at threonine 217

Drugs targeting this molecule or its formation typically act by inhibiting tau kinases (e.g., GSK-3β), promoting tau dephosphorylation via phosphatase activation, reducing total tau expression through antisense oligonucleotides (ASOs), or utilizing monoclonal antibodies to clear pathological tau species and prevent their propagation.