The role of tau phosphorylation and cleavage in neuronal cell death

The microtubule-associated protein tau is the primary component of the intracellular filamentous deposits found in Alzheimer's disease (AD) brain and also in a family of neurodegenerative diseases called 'tauopathies', where tau pathology is the primary, defining characteristic with little or no amyloid-beta (Abeta) pathology. It has been demonstrated that tau modifications such as hyperphosphorylation and truncation might be important events in the process leading to tau intracellular aggregation and neuronal cell death. The discovery of tau gene mutations in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) reinforced the predominant role attributed to tau proteins in the pathogenesis of neurodegenerative disorders. This review highlights recent findings concerning the normal metabolism and function of tau, as well as the abnormal processing and function of tau in AD and in the tauopathies.