MAPT

About MAPT

MAPT on chromosome 17q21.31 encodes tau, a microtubule associated protein abundant in neuronal axons that promotes the assembly and stability of microtubules. Alternative splicing of exons 2, 3, and 10 produces six isoforms in the adult brain, with either three or four microtubule binding repeats, called 3R and 4R tau. In disease, tau becomes abnormally phosphorylated, detaches from microtubules, and aggregates into filaments. Tau aggregates are found in a group of disorders called tauopathies, including Alzheimer disease, where they form neurofibrillary tangles together with amyloid plaques, as well as frontotemporal lobar degeneration, progressive supranuclear palsy, corticobasal degeneration, Pick disease, and chronic traumatic encephalopathy. In 1998 MAPT mutations were identified as the cause of frontotemporal dementia with parkinsonism linked to chromosome 17, demonstrating that tau dysfunction alone can cause neurodegeneration. Many of these mutations alter splicing of exon 10 and the balance of 3R and 4R tau. The MAPT region contains a large inversion that defines two haplotypes, H1 and H2, and H1 is associated with increased risk of progressive supranuclear palsy, corticobasal degeneration, and Parkinson disease. The spread of tau pathology through brain regions follows a pattern described by Braak staging. Anti tau antibodies, antisense oligonucleotides, and aggregation inhibitors are in clinical trials, with mixed results so far.