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

Pathological aggregated tau refers to the abnormal accumulation of the microtubule-associated protein tau (MAPT) into insoluble structures such as paired helical filaments and neurofibrillary tangles. In its healthy state, tau is a soluble protein that promotes the assembly and stability of microtubules, which are essential for axonal transport and neuronal structural integrity. However, in tauopathies like Alzheimer's disease, tau undergoes post-translational modifications—most notably hyperphosphorylation—that cause it to detach from microtubules and self-assemble into toxic oligomers and aggregates. These aggregates disrupt cellular processes, impair synaptic function, and eventually lead to neuronal death, with the spread of tau pathology correlating closely with cognitive decline. Therapeutic strategies targeting pathological tau include monoclonal antibodies designed to clear extracellular tau seeds, small molecule inhibitors to prevent aggregation, and antisense oligonucleotides to reduce total tau production. Additionally, tau-specific PET tracers and fluid biomarkers have become critical tools for diagnosing disease progression and monitoring the efficacy of these tau-directed therapies in clinical trials.

Other names

Pathological tauNeurofibrillary tangles (NFTs)Paired helical filaments (PHFs)Tau oligomersHyperphosphorylated tauMAPT aggregates

Aggregation inhibition, microtubule stabilization, monoclonal antibody-mediated clearance, antisense oligonucleotide (ASO) mediated knockdown of MAPT mRNA, and kinase inhibition to reduce hyperphosphorylation.