Going new places using an old MAP: tau, microtubules and human neurodegenerative disease

The microtubule-associated protein tau was originally identified as a protein that co-purified with tubulin in vitro, stimulated assembly of tubulin into microtubules and strongly stabilized microtubules. Recognized now as one of the most abundant axonal microtubule-associated proteins, a convergence of evidence implicates an overlapping in vivo role of tau with other axonal microtubule-associated proteins (e.g. MAP1B) in establishing microtubule stability, axon elongation and axonal structure. Missense and splice-site mutations in the human tau gene are now known to be causes of inherited frontotemporal dementia and parkinsonism linked to chromosome 17, a cognitive disorder of aging. This has provided direct evidence for the hypothesis that aberrant, filamentous assembly of tau, a frequent hallmark of a series of human cognitive diseases, including Alzheimer's disease, can directly provoke neurodegeneration.