Abstract
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques. In this study, we analyzed postmortem brain tissues from five institutionalized patients with schizophrenia and history of surgical leucotomy with subsequent survival of at least another 40 years. Because leucotomy involves severing axons bilaterally in prefrontal cortex, this surgical procedure represents a human model of single traumatic brain injury with severe axonal damage and no external impact. We examined cortical tissues at the leucotomy site and at both prefrontal cortex rostral and frontal cortex caudal to the leucotomy site. For comparison, we analyzed brain tissues at equivalent neuroanatomical sites from non-leucotomized patients with schizophrenia, matched in age and gender. All five leucotomy cases revealed severe white matter damage with dense astrogliosis at the axotomy site and also neurofibrillary tangles and p-tau immunoreactive neurites in the overlying gray matter. Four cases displayed p-tau immunoreactivity in neurons, astrocytes and cell processes encompassing blood vessels at cortical sulcal depths in irregular patterns, similar to CTE. The three cases with apolipoprotein E ε4 haplotype showed scattered β-amyloid plaques in the overlying gray matter, but not the two cases with apolipoprotein E ε3/3 genotype. Brain tissue samples from prefrontal cortex rostral and frontal cortex caudal to the leucotomy site, and all cortical samples from the non-leucotomized patients, showed minimal p-tau and β-amyloid pathology. These findings suggest that chronic axonal damage contributes to the unique pathology of CTE over time.
Highlights
In 2010 an estimated 2.5 million persons suffered from traumatic brain injury (TBI) in the United States, of whom 50,000 died from the injury and another 2,80,000 required hospitalization [36]
Brain tissue samples from prefrontal cortex rostral and frontal cortex caudal to the leucotomy site, and all cortical samples from the non-leucotomized patients, showed minimal p-tau and β-amyloid pathology. These findings suggest that chronic axonal damage contributes to the unique pathology of Chronic traumatic encephalopathy (CTE) over time
We identified a human model that isolates the axonal damage component of TBI, that is, surgical leucotomy, and tested the hypothesis that chronic axonal injury can result in neurodegenerative changes, such as neurofibrillary tangles (NFTs) and β-amyloid plaques
Summary
In 2010 an estimated 2.5 million persons suffered from traumatic brain injury (TBI) in the United States, of whom 50,000 died from the injury and another 2,80,000 required hospitalization [36]. TBI is a known environmental risk factor for the development of dementia later in life. Multiple studies provide evidence that single moderate or severe TBI increases the likelihood of eventual presentation with clinical signs and symptoms of neurodegeneration, such as Alzheimer Disease (AD) [7, 29, 35]. Such studies typically did not include postmortem examinations of brain tissues. Whether single mild TBI (concussion) confers increased risk of developing dementia with neuropathological abnormalities in susceptible individuals remains undetermined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
