The Role of Tau Phosphorylation in the Pathogenesis of Alzheimer's Disease

The microtubule-associated protein tau, which is abundantly expressed in neurons, is deposited in cells in an abnormally phosphorylated state as fibrillar lesions in numerous neurodegenerative diseases, with the most notable being Alzheimer's disease. Tau plays a crucial role in the neuron as it binds and stabilizes microtubules, and can regulate axonal transport; functions that are regulated by site-specific phosphorylation events. In pathological conditions such as Alzheimer's disease and other tauopathies, tau is abnormally phosphorylated, and that this contributes to its dysfunction. Given the increasing evidence that a disruption in the normal phosphorylation state of tau followed by conformational changes plays a key role in the pathogenic events that occur in Alzheimer's disease and other tauopathies; it is critical to elucidate the regulation of tau phosphorylation. This review focuses on recent literature pertaining to the regulation of tau phosphorylation and function, and the role that a dysregulation of tau phosphorylation may play in the neuronal dysfunction in Alzheimer's disease.