Microtubule-associated protein tau (MAPT) amyloid aggregates (Tau aggregates)

Microtubule-associated protein tau (MAPT) is a phosphoprotein that plays a vital role in stabilizing neuronal microtubules, which are essential for maintaining cell structure and facilitating intracellular transport [UniProt: P10636]. In neurodegenerative diseases collectively termed tauopathies, tau protein undergoes abnormal post-translational modifications, most notably hyperphosphorylation, which causes it to detach from microtubules and self-assemble into toxic oligomers and insoluble amyloid aggregates [PubMed: 32839610]. These aggregates, including paired helical filaments (PHFs) and neurofibrillary tangles (NFTs), disrupt cellular homeostasis and spread through the brain in a prion-like manner, closely correlating with the progression of cognitive impairment [PubMed: 29101315]. Therapeutic interventions targeting tau aggregates include monoclonal antibodies designed to intercept extracellular tau seeds, small molecules that inhibit the aggregation process, and antisense oligonucleotides (ASOs) aimed at reducing total tau levels [PubMed: 34635441]. Despite several clinical trial failures, tau remains a primary target for Alzheimer's disease and related dementias due to its direct link to neurodegeneration [PubMed: 30305916].

Other names

Neurofibrillary tanglesPaired helical filamentsPHF-tauTau oligomersMAPT aggregatesTau amyloid

Therapeutic strategies include the use of monoclonal antibodies to clear extracellular tau seeds, small molecule aggregation inhibitors to prevent the formation of neurofibrillary tangles, and antisense oligonucleotides to reduce overall tau expression levels [PubMed: 34635441].