Over 1.7 million Americans suffer a traumatic brain injury each year, and beyond the immediate effects, growing evidence demonstrates that a single traumatic brain injury, or TBI, may initiate long term processes that further damage the brain. TBI is an established risk factor for later development of cognitive impairments, such as Alzheimer’s disease. In boxing, this is called “punch-drunk” syndrome.
Douglas Smith, MD, professor of Neurosurgery and director of the Center for Brain Injury and Repair at Penn’s Perelman School of Medicine states:
“A single traumatic brain injury is very serious, both initially, and as we’re now learning, even later in life. Plaques and tangles are appearing abnormally early in life, apparently initiated or accelerated by a single TBI.”
The researchers found both tau tangles and amyloid-beta plaques in survivors, years after a single moderate-to-severe TBI. In repetitive head injury, previous studies have shown a tau accumulation as the signature pathology of a condition called chronic traumatic encephalopathy. In studies of people less than 4 weeks after dying from a single TBI, no similar tau pathology was found. In addition, while widespread amyloid-beta plaques have been found in about 30 percent of people shortly after injury, previous work showed that plaques disappeared within months.
he traditional understanding is that tau binds to microtubules and assists with their formation and stabilization. However when tau is hyperphosphorylated, it is unable to bind and the microtubules become unstable and begin disintegrating. The unbound tau clumps together in formations called neurofibrillary tangles.
More explicitly, intracellular lesions known as pretangles develop when tau is phosphorylated excessively and on improper amino acid residues. These lesions, over time, develop into filamentous neurofibrilary tangles (NFTs) which interfere with numerous intracellular functions.
TBI survivors showed a high density and wide distribution of neurofibrillary tau tangles and amyloid-beta plaque pathology far beyond what was found in controls. Specifically, about a third of the cases showed tangle pathology years after a single TBI, similar in appearance to the tangles found after repetitive TBI and in neurodegenerative diseases such as Alzheimer’s disease. Moreover, the amyloid-beta plaques were not only found years after TBI, but the majority of cases displayed diffuse as well as “neuritic” plaques with the same character as “senile” plaques also found in Alzheimer’s disease. This suggests that years after a single TBI, amyloid-beta plaques may return and become neuritic.
Researchers examined post-mortem brains from 39 long-term survivors of a single TBI, extending the survival time from 1-47 years survival after TBI, and compared them to uninjured, age-matched controls.
The present findings, showing that two hallmark pathologies of Alzheimer’s disease can be found years after a single TBI, may provide a pathological link with the epidemiological observation of an increased risk of developing Alzheimer’s disease. Moreover, future research to better understand this long-term neurodegenerative process after a single TBI may reveal important targets for treatment with emerging anti-tau and anti-amyloid therapies.
While TBI does not routinely lead to accelerated NFT formation, further work may determine if other blood components or factors unrelated to hemorrhages are involved in this TBI induced augmentation of tau pathology. NFTs are most commonly seen associated with repetitive mild TBI as opposed to one instance of severe traumatic brain injury however.
Sources:
Written by Sy Kraft