. Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery. 2006 Nov 1;59(5):1086-92; discussion 1092-3. PubMed.


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  1. A major contribution of this report is that it sharply focuses attention on the potentially deleterious effects of repeated head trauma in contact sports. The neuropathological findings are consistent with previous reports of what was termed "dementia pugilistica." It is certainly possible that the erratic fluctuations in mood and the severe depression with multiple suicide attempts relate to the widespread cortical and subcortical neuritic pathology. It also is possible that the abnormal behaviors in life resulted from unrelated psychopathology that may or may not have been exacerbated by steroid use. The authors correctly consider these alternatives, and make a much-needed call to systematically conduct clinico-pathological studies of individuals involved in these contact sports. The clear demonstration that neuropathological lesions can be associated with such sports underscores the paucity of data regarding the possible neuropsychiatric consequences. Full understanding of these consequences is needed to implement appropriate measures to ensure the safety of the participants.

  2. We have argued for some years that neurofibrillary pathology, such as tangles and dystrophic neurites, are not particularly Alzheimer disease-specific, as they represent the prolonged aberrant reaction of nerve cells to ongoing or repeated structural injury (Vickers et al., 2000). In the case of “garden-variety” Alzheimer disease, we have proposed that plaque formation may cause enough compression of the neuropil to effectively squeeze axons. This would result in the stimulation of the stereotypical reaction to such interruption in axoplasmic flow, including the abnormal regenerative changes throughout the nerve cell that ultimately lead to classic neurofibrillary pathology.

    In this regard, any prolonged or repeated structural injury to axons, as you see in younger people with repeated head injury (e.g., Hof et al., 1991), would be predicted to have a similar outcome. This may be why the early axonal pathology associated with plaque formation is easy to model in experimental models involving axonal shear or transection (Dickson et al., 2000; Chung et al., 2005; Dickson et al., 2005). However, true neurofibrillary pathology may take a much longer time to develop, as it relies on the perikaryal response that builds up due to the prolonged or repeated axonal injury. In this regard, most neurofibrillary tangles in the neocortex in Alzheimer disease are still intracellular, further indicating a long period of time leading to degeneration. I would be interested in this report about more detail on the type of axonal pathology still present, and also if the tangles were largely intracellular.


    . Sequence of cellular changes following localized axotomy to cortical neurons in glia-free culture. J Neurotrauma. 2000 Nov;17(11):1095-103. PubMed.

    . alpha-Internexin immunoreactivity reflects variable neuronal vulnerability in Alzheimer's disease and supports the role of the beta-amyloid plaques in inducing neuronal injury. Neurobiol Dis. 2005 Mar;18(2):286-95. PubMed.

    . Mild axonal stretch injury in vitro induces a progressive series of neurofilament alterations ultimately leading to delayed axotomy. J Neurotrauma. 2005 Oct;22(10):1081-91. PubMed.

    . Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol. 1991;82(4):321-6. PubMed.

    . The cause of neuronal degeneration in Alzheimer's disease. Prog Neurobiol. 2000 Feb;60(2):139-65. PubMed.

    View all comments by James Vickers
  3. Repeated traumatic brain injury (TBI) in tau transgenic mice variably induces accelerated tangle formation. Moreover, the evidence that TBI is a robust risk factor for AD is very strong; see Yoshiyama et al., 2005.


    . Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model. J Neurotrauma. 2005 Oct;22(10):1134-41. PubMed.

  4. Note from the Alzforum editor: Today's New York Times followed up its initial article of 18 January on neurodegenerative consequences of repeated concussions in professional football with the story of yet another player. According to the NYT, Ted Johnson, the New England Patriot's middle linebacker until his retirement in 2005, forgets people's names, misses appointments, and suffers from depression. Johnson sustained repeated concussions in close succession in 2002. The news article cites Johnson's neurologist as saying that Johnson shows the cognitive impairment that is characteristic of early Alzheimer disease. Johnson is 34 years old.

    View all comments by Gabrielle Strobel
  5. Given the similarities between Alzheimer disease and dementia pugilistica, we studied retired boxers in the late 1990s. We found that when we standardized for technical knockouts, boxers who were becoming demented were the ones who carried ApoE4 alleles, just as one might predict (Jordan et al., 1997). This raises the question of whether boxers and footballers should be genotyped before committing to a career in these sports. Neither the boxing nor football associations welcome this prospect.

    We also published a case report of a famous boxer, whose name we are not at liberty to disclose, who died of amyloid angiopathy (Jordan et al., 1995). From the perspective of the field of neurodegeneration research, the link between repeated mild brain trauma and degenerative changes in subsequent years is beyond dispute.


    . Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA. 1997 Jul 9;278(2):136-40. PubMed.

    . Apolipoprotein E epsilon 4 and fatal cerebral amyloid angiopathy associated with dementia pugilistica. Ann Neurol. 1995 Oct;38(4):698-9. PubMed.

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