The microtubule-associated protein tau is a scaffolding protein found mainly in neurons, where it is enriched in axons.
Under physiological conditions, tau is post-translationally modified at many sites by primarily phosphorylation, however under pathological conditions, there is an even higher degree of modification, rendering tau aggregation-prone and impairing its clearance. This in turn can impair brain function and to cause neurodegeneration. Tau contains a high content of proline and lysine residues, and 85 potential phosphorylation sites and the high proline and lysine content probably facilitates pathological crosslinking and aggregation with other tau molecules.
Intracellular tau aggregates known as neurofibrillary tangles are a hallmark of Alzheimer disease, together with extracellular deposits of amyloid β. Imaging studies suggest that tau is a better predictor of the symptoms of dementia than measures of Aβ.
Intracellular aggregates of tau are also the defining feature of the group of neurological disorders known as tauopathies, such as familial frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Other disorders that involve tau pathology are traumatic brain injury.