The tau proteins are the product of alternative splicing from a single gene that in humans is designated MAPT (microtubule-associated protein tau) and is located on chromosome 17. In humans, these proteins are found mostly in neurons compared to non-neuronal cells. One of tau’s main functions is to modulate the stability of axonal microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes. Tau proteins interact with tubulin to stabilize microtubules and promote tubulin assembly into microtubules. Through its isoforms and phosphorylation tau protein interacts with tubulin to stabilize microtubule assembly.

Pathologies and dementias of the nervous system such as Alzheimer’s disease and Parkinson’s disease are associated with tau proteins that have become defective and no longer stabilize microtubules properly. Hyperphosphorylation of the tau protein (tau inclusions, pTau) can result in the self-assembly of tangles of paired helical filaments and straight filaments, which are involved in the pathogenesis of Alzheimer’s disease, frontotemporal dementia, and other tauopathies. When misfolded, this otherwise very soluble protein can form extremely insoluble aggregates that contribute to a number of neurodegenerative diseases. Mutations that alter function and isoform expression of tau lead to hyperphosphorylation, which in turn disassembles microtubules and sequesters normal tau, MAP 1, MAP 2, and ubiquitin into neurofibrillary tangles, which are composed of paired helical filaments (PHF).These insoluble structures damage cytoplasmic functions and interferes with axonal transport, which can lead to cell death.