Microtubule-associated protein tau aggregate (Tau aggregate (or MAPT aggregate, though "tau" is most common))

Microtubule-associated protein tau is a neuronal protein primarily responsible for stabilizing microtubules within axons by binding at specific sites on tubulin heterodimers. Under physiological conditions, it promotes microtubule assembly and maintains neuronal polarity. In pathological states—such as Alzheimer’s disease—tau becomes hyperphosphorylated and dissociates from microtubules, leading to its aggregation into insoluble fibrillar structures known as neurofibrillary tangles or paired helical filaments. These aggregates disrupt cellular function and are a hallmark feature across multiple neurodegenerative disorders termed “tauopathies.” The process by which soluble intrinsically disordered monomeric tau transitions into highly ordered amyloid-like fibrils is influenced by post-translational modifications and environmental factors such as pH and ionic strength. Targeting these pathogenic aggregates has become a major therapeutic strategy for modifying disease progression in Alzheimer’s disease and related disorders.

Other names

Tau protein aggregateNeurofibrillary tangle (when referring to the pathological structure)Paired helical filament tau (PHF-tau)MAPT aggregateHyperphosphorylated tau aggregate

Drugs targeting tau aggregates act via several mechanisms including: Inhibition of aggregation/fibrillization of tau proteins; Promotion of disaggregation or clearance of existing aggregates/neurofibrillary tangles; Immunotherapy to promote immune-mediated clearance via anti-tau antibodies