Tau and axonopathy in neurodegenerative disorders.

The microtubule (MT)-associated protein (MAP) tau in neurons has been implicated as a significant factor in the axonal growth, development of neuronal polarity, and the maintenance of MT dynamics. Tau is localized to the axon, and is known to promote MT assembly and to stabilize axonal MTs. These functions of tau are primarily regulated by the activities of protein kinases and phosphatases. In Alzheimer's disease and other neurodegenerative disorders, abundant filamentous tau inclusions are found to be major neuropathological characteristics of these diseases. Both somato-dendritic and axonal tau lesions appear to be closely associated with axonal disruption. Furthermore, recent discoveries of pathogenic mutations on the tau gene suggest that abnormalities of tau alone are causative of neurodegeneration. Finally, analyses of transgenic mice that express human tau proteins have enabled in vivo quantitative assessments of axonal functions and have provided information about mechanistic relationships between pathological alteration of tau and axonal degeneration.