Tau, where are we now?

Tau is a multifunctional protein that was originally identified as a microtubule-associated protein. Tau is primarily a neuronal protein, but it is becoming increasingly evident that tau is present in non-neuronal cells where it also plays important roles. Tau is the primary protein component of the filaments (both paired helical and straight filaments) found in Alzheimer's disease brain. Further there is an ever growing family of neurodegenerative diseases called "tauopathies" where tau pathology is the primary, defining characteristic with little or no Abeta pathology. These findings, along with the fact that mutations in the tau gene cause a group of diseases collectively known as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), clearly demonstrate that tau dysfunction results in neuronal dysfunction and death. This review highlights recent findings concerning the normal metabolism and function of tau, as well as the abnormal processing and function of tau in Alzheimer's disease and in the tauopathies, both sporadic and familial.