Tau Pathology: A Selected View on the Current Status

Tau (tubulin associated unit) is a microtubule regulatory protein forming pathological aggregates in multiple neurodegenerative disease termed tauopathies. Microtubules are key cytoskeletal elements found in all eukaryotic cells, comprising the mitotic spindle in dividing cells and the skeleton and transport system of the nerve cell. The polymerized microtubule shaft (a hollow cylinder of ∼250 nm) is composed of the heterodimer protein, tubulin. Microtubules are decorated with multiple microtubule associated regulatory proteins (MAPs). Tau (MAPT), among the first microtubule associated proteins to be identified, was implicated in microtubule initiation as well as assembly, with increased expression in neurons and specific association with axonal microtubules. Alzheimer's disease (AD) is the most prevalent tauopathy, exhibiting tau-neurofibrillary tangles associated with cognitive dysfunction. AD is also characterized by β-amyloid plaques. An abundance of tau inclusions, in the absence of β-amyloid deposits, can be found in Pick's disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases, collectively described as tauopathies. The increase in tau pathology in AD correlates with the associated cognitive decline. This book chapter is an update on several recent reviews. It is not a comprehensive review of the literature, but rather an updating point of view.