Microtubule-associated protein tau paired helical filaments (Tau PHFs)

Microtubule-associated protein tau (MAPT) is a critical protein that stabilizes axonal microtubules in the central nervous system (UniProt: P10636). In Alzheimer's disease (AD), tau becomes hyperphosphorylated and dissociates from microtubules, misfolding into pathological 3R/4R paired helical filaments (PHFs) (PubMed: 28678769). These PHFs are the primary component of neurofibrillary tangles (NFTs), which are a hallmark of AD and correlate closely with the severity of cognitive impairment (PubMed: 32730231). The 3R and 4R designations refer to the number of microtubule-binding repeats (three or four) included in the tau isoforms that constitute the filaments (PubMed: 30143501). Therapeutic interventions targeting these filaments aim to inhibit their formation, promote their clearance through monoclonal antibodies, or reduce overall tau expression using antisense oligonucleotides (PubMed: 34635803). Current drug development efforts focus on preventing the seeding and spread of tau pathology across brain regions to halt neurodegeneration (PubMed: 31061481).

Other names

Neurofibrillary tanglesPHF-tauTau aggregates3R/4R tau filamentsNFTsPathological tau filaments

Inhibition of tau-tau interaction to prevent filament assembly, monoclonal antibody-mediated clearance of extracellular tau seeds to prevent propagation, and antisense oligonucleotide-mediated reduction of tau protein synthesis (PubMed: 34635803, PubMed: 31061481).