Toxic tau: structural origins of tau aggregation in Alzheimer's disease

Alzheimer's disease is characterized by the extracellular accumulation of the amyloid β in the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles. Most of the Alzheimer's drugs targeting amyloid β have been failed in clinical trials. Particularly, tau pathology connects greatly in the pathogenesis of Alzheimer's disease. Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron. Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved. The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its…