Progressive accumulation of hyperphosphorylated microtubule associated protein tau in to neurofibrillary tangles and neuropil threads can be a common feature of numerous neurodegenerative tauopathies, including Pick disease, Alzheimer disease, ubiquitin conjugating progressive supranuclear palsy, and frontotemporal dementias. Tau pathology in addition has been documented in individuals who suffered from just one severe traumatic brain injury or multiple slight, concussive injuries. Particularly, severe axonal accumulations of complete and phospho tau have been noted within hours to months, while NFTs have been noticed years following simple severe TBI in humans. Furthermore, NFT pathology is common in patients with life time histories of multiple concussive injuries. Tau pathologies in AD and TBI share similar immunohistochemical and bio-chemical characteristics. In both circumstances, somatodendritic tau immunoreactivity is outstanding, but, PTM tau immunoreactive neurites noticed in TBI have been suggested to have an axonal origin, which might be distinct from the threadlike forms in AD suggested to become dendritic in origin. Furthermore, the anatomical distribution of NFTs might be unique following TBI than is typically observed in AD. Thus, the mechanisms resulting in tau hyperphosphorylation in TBI varies from those in AD. The biological function of tau would be to stabilize microtubules. Tau presenting to MTs is controlled by phosphorylation. Abnormally phosphorylated tau has paid off MT binding, which results in MT destabilization. This in turn may compromise normal cytoskeletal function, fundamentally resulting in axonal and neuronal degeneration. This is actually the foundation for the hypothesis that tau hyperphosphorylation leads to neurodegeneration in tauopathies. Identification of several mutations in the tau gene, which cause frontotemporal Chk inhibitor dementia with parkinsonism linked to chromosome 17 and lead to tau hyperphosphorylation, supports this hypothesis. Results from experimental designs where human mutant tau is expressed give further support for this hypothesis. In these types, hyperphosphorylation of tau generally precedes axonopathy and degeneration. Therefore, targeting tau both by reducing its phosphorylation state or location is a target of pre-clinical beneficial growth for AD and related dementias. Two major systems proposed to underlie tau hyperphosphorylation are aberrant activation of kinases and downregulation of protein phosphatases. Cyclin dependent kinase 5 and its co activator p25, glycogen synthase kinase 3B, and protein phosphatase 2A have already been implicated in hyperphosphorylation of tau in vivo. The others such as protein kinase A, extra-cellular signal regulated kinase 1/2, and c Jun N final kinase have only been shown to manage tau phosphorylation in vitro. It’s unknown whether these kinases and phosphatase bring about TBI activated tau pathology. We previously noted that controlled cortical impact TBI accelerated tau pathology in young 3 Tg AD mice.