Microtubule-associated protein tau (MAPT) (Tau)

Microtubule-associated protein tau (MAPT) is a primary structural protein in the central nervous system that stabilizes microtubules, which are essential for axonal transport and neuronal integrity (UniProt P10636). In pathological conditions such as Alzheimer's disease and other tauopathies, tau becomes hyperphosphorylated and dissociates from microtubules, leading to the formation of toxic soluble oligomers and insoluble neurofibrillary tangles (Wang & Mandelkow, 2016, Nature Reviews Neuroscience). These pathological species are thought to spread through the brain in a prion-like manner, moving from neuron to neuron and driving progressive neurodegeneration (Goedert et al., 2017, Science). Because the accumulation of tau pathology correlates strongly with cognitive decline, it has become a major therapeutic target. Current strategies include monoclonal antibodies designed to intercept extracellular tau seeds, small molecules that inhibit tau aggregation, and antisense oligonucleotides (ASOs) that reduce the overall production of tau protein (Mullard, 2021, Nature Reviews Drug Discovery). Clinical trials are ongoing to determine if clearing these pathological species can slow or halt the progression of dementia and other motor-related tauopathies.

Other names

Tau aggregatesNeurofibrillary tanglesNFTsPaired helical filamentsPHFsHyperphosphorylated tauTau oligomersTau pathological species

Mechanisms include passive immunotherapy using monoclonal antibodies to neutralize extracellular tau seeds, active immunotherapy (vaccines) to induce an endogenous immune response, small molecule inhibitors of tau aggregation, and antisense oligonucleotides (ASOs) to reduce total tau expression.