Microtubule-associated protein tau (aggregated) (PHF-tau)

Aggregated paired helical filament tau (PHF-tau) is the primary constituent of neurofibrillary tangles (NFTs), a hallmark pathological feature of Alzheimer's disease and other tauopathies (Gao et al., 2018, PubMed: 30126344). In its healthy state, tau is a soluble microtubule-associated protein (MAPT) that stabilizes microtubules in axons, facilitating intracellular transport (UniProt: P10636). However, in disease states, tau undergoes hyperphosphorylation and misfolding, leading to the formation of insoluble paired helical filaments that aggregate into NFTs within neurons (NIH, 2023). These aggregates disrupt cellular function, impair axonal transport, and are strongly correlated with cognitive decline and neurodegeneration (Schöll et al., 2019, PubMed: 30643015). Therapeutic strategies targeting PHF-tau include small molecule aggregation inhibitors like LMTM, tau-directed monoclonal antibodies such as semorinemab designed to clear extracellular "seeds," and antisense oligonucleotides to reduce total tau production (Mullard, 2021, Nature Reviews Drug Discovery). Additionally, PHF-tau serves as a critical diagnostic target for positron emission tomography (PET) imaging agents like flortaucipir, which allow for the visualization of tau pathology progression in living patients (FDA, 2020).

Other names

Neurofibrillary tanglesNFTPaired helical filamentsTau protein aggregatesHyperphosphorylated tau aggregatesAggregated tau

Inhibition of tau aggregation, monoclonal antibody-mediated clearance of extracellular tau seeds, and reduction of tau hyperphosphorylation or total tau expression.