Aggregated paired helical filament tau (PHF-tau) (PHF-tau)

Aggregated paired helical filament tau (PHF-tau), which forms neurofibrillary tangles (NFTs), is a primary pathological hallmark of Alzheimer's disease and various other neurodegenerative disorders known as tauopathies. In a healthy state, tau is a soluble protein that promotes microtubule assembly and stability within axons; however, pathological hyperphosphorylation causes tau to detach from microtubules and misfold into insoluble filaments. These filaments aggregate into NFTs, which disrupt cellular transport mechanisms and eventually lead to synaptic loss and neuronal death. Therapeutic interventions targeting PHF-tau include monoclonal antibodies designed to intercept the 'seeding' of tau between neurons and small molecules intended to inhibit the aggregation process or promote the clearance of existing tangles. Because the density and distribution of these aggregates correlate strongly with cognitive decline, they serve as critical targets for both disease-modifying therapies and diagnostic neuroimaging.

Other names

Neurofibrillary tanglesNFTsTau aggregatesHyperphosphorylated tau aggregatesPaired helical filamentsMisfolded tau protein

Inhibition of tau aggregation, disaggregation of existing paired helical filaments, antibody-mediated clearance of extracellular tau seeds to prevent trans-synaptic spreading, and selective binding for PET imaging visualization.