Pathological tau aggregate

Pathological tau aggregates are abnormal assemblies of the tau protein, typically characterized by hyperphosphorylation, truncation, or other post-translational modifications that lead to loss of its physiological role in microtubule stabilization and gain of toxic, aggregation-prone properties[1][2][4][7]. In neurodegenerative diseases collectively called tauopathies—including Alzheimer’s disease, frontotemporal dementia, and progressive supranuclear palsy—tau protein forms insoluble aggregates such as paired helical filaments and neurofibrillary tangles inside neurons[2][5][7]. These aggregates are thought to promote neurodegeneration by disrupting intracellular transport, impairing synaptic and cytoskeletal integrity, and spreading in a self-propagating, prion-like manner[1][3][5]. Numerous post-translational modifications including hyperphosphorylation (at sites such as serine 396 and serine 404), truncation, acetylation, and ubiquitination are implicated in the formation of pathological tau aggregates[1][2][4]. The progression and levels of tau aggregation closely track with the severity of cognitive decline, making pathological tau aggregates primary molecular targets for therapeutic interventions such as monoclonal antibodies and aggregation inhibitors[2][6][7]. Detection and quantification of pathological tau and its phosphorylated forms in cerebrospinal fluid or by PET imaging serve as disease biomarkers[5][7]. Safety challenges for targeting pathological tau aggregates include possible immune-related adverse events, technical barriers to delivery, and limited clinical benefit in advanced disease stages[6].

Other names

tau aggregatepathological tautau tangleneurofibrillary tangleNFTpTau aggregatehyperphosphorylated tau aggregatetau filamentpaired helical filament

Antibody-mediated clearance (immunotherapy), Inhibition of aggregation, Promotion of aggregate disassembly, Stabilization of native tau