Microtubule-associated protein tau (MAPT) (MAPT)

Microtubule-associated protein tau (MAPT) is a phosphoprotein that plays a vital role in stabilizing neuronal microtubules, which are essential for axonal transport and structural integrity (UniProt P10636). In Alzheimer's disease, tau becomes hyperphosphorylated, causing it to dissociate from microtubules and aggregate into insoluble paired helical filaments and neurofibrillary tangles (PubMed 33024317). These aggregates are closely linked to neurodegeneration and the progression of cognitive symptoms, serving as a hallmark of the disease alongside amyloid-beta plaques. Therapeutic approaches targeting tau include small molecule aggregation inhibitors, monoclonal antibodies designed to neutralize extracellular tau seeds to prevent spread, and antisense oligonucleotides that reduce overall tau production (PubMed 31433444). Despite numerous clinical trials, many anti-tau therapies have struggled to demonstrate clinical efficacy, possibly due to the difficulty of targeting the most toxic intracellular species or initiating treatment too late in the disease course. Monitoring these therapies relies heavily on biomarkers such as phosphorylated tau levels in cerebrospinal fluid and positron emission tomography (PET) imaging to visualize aggregate burden in the brain (PubMed 31433444).

Other names

TauNeurofibrillary tanglesPaired helical filamentsPHF-tauMAPT protein

Inhibition of tau aggregation, antibody-mediated clearance of extracellular tau seeds, and antisense oligonucleotide-mediated reduction of tau protein expression.