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

Microtubule-associated protein tau (MAPT) is a phosphoprotein that primarily functions to stabilize microtubules in the central nervous system, supporting axonal transport and neuronal architecture (UniProt P10636). In pathological states collectively termed tauopathies, tau becomes hyperphosphorylated and dissociates from microtubules, subsequently misfolding into insoluble paired helical filaments and neurofibrillary tangles (NFTs) (NIH, 2023). These aggregated forms are neurotoxic and their spatial distribution in the brain closely correlates with the severity of cognitive impairment in Alzheimer's disease and other dementias (PubMed, PMID: 33028158). Therapeutic interventions targeting these aggregates include monoclonal antibodies like semorinemab and bepranemab, which aim to intercept the 'seeding' of tau between neurons, and small molecules like hydromethylthionine mesylate (LMTM) designed to inhibit aggregation (ClinicalTrials.gov). Additionally, antisense oligonucleotides are being explored to reduce the overall production of tau protein to prevent further accumulation. Despite their promise, targeting tau presents challenges such as ensuring blood-brain barrier penetration and avoiding the disruption of normal tau's physiological role in microtubule stability (Nature Reviews Drug Discovery, 2021). Monitoring efficacy often involves advanced PET imaging and fluid-based biomarkers that track tau pathology progression.

Other names

Neurofibrillary tanglesNFTsPaired helical filamentsPHFsTau aggregatesTau fibrilsMisfolded tau

Aggregation inhibition, Immunotherapy-mediated clearance, Antisense oligonucleotide-mediated knockdown