Journal
JOURNAL OF NEUROTRAUMA
Volume 30, Issue 11, Pages 981-997Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2012.2699
Keywords
adult brain injury; axonal injury; immunoblots; neurodegenerative disorders; traumatic brain injury
Funding
- The National Institute on Aging [R01 AG019795, P30 AG19610]
- State of Arizona Alzheimer's Disease Research Consortium
- National Institute of Neurological Disorders and Stroke [U24 NS0702026]
- Arizona Department of Health Services [211002]
- Arizona Biomedical Research Commission [4001, 011, 05-901, 1001]
- Michael J. Fox Foundation for Parkinson's Research
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Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neuro-degenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in the brains of former boxers with neuropathologically confirmed DP. Our experiments revealed biochemical and cellular alterations in DP that are complementary to and extend information already provided by histological methods. ELISA and one-dimensional and two dimensional Western blot techniques revealed differential expression of select molecules between three patients with DP and three age-matched non-demented control (NDC) persons without a history of TBI. Structural changes such as disturbances in the expression and processing of glial fibrillary acidic protein, tau, and alpha-synuclein were evident. The levels of the A beta-degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-beta levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital.
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