Tau oligomers can occur in human brains within days of a single traumatic brain injury

Traumatic brain injury (TBI) is a major risk factor for Alzheimers disease (AD), yet the early molecular events linking the two remain unclear. Neurofibrillary tangles (NFTs), a hallmark of AD, are observed in individuals with a history of single or repetitive head injury. Animal studies show that tau oligomers, the toxic species preceding the NFTs, appear shortly after TBI, but corresponding human data are lacking. Here, we investigated tau changes in the brains of individuals who died shortly after TBI compared to those surviving long-term. We report abnormal tau oligomers in the brain of short-term survivors whereas NFTs were the main feature in long-term survivors. These findings support a model where TBI triggers early tau oligomers formation that spread through a prion-like mechanism, seeding tau pathology and contributing to late-onset AD. The novel identification of tau oligomers in acute TBI reveals potential early disease mechanisms and therapeutic targets for AD prevention. Importance statementBy revealing a potential early disease mechanism of Alzheimers disease (AD), this study represents a major breakthrough in our understanding, treatment and prevention of the disease. To our knowledge, this is the first report of tau oligomers in the brain of individuals suffering acute Traumatic Brain Injury (TBI). This is an important finding considering that TBI is a major risk factor of AD and tau oligomers are thought to be the most toxic species preceding tau pathology, a characteristic signature of AD. The identification of these early tau-related events after TBI provides insight into potential early AD mechanisms and offers a unique opportunity for early therapeutic intervention and prevention.