Neurochemical Profile of Dementia Pugilistica

Abstract

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 neurodegenerative 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 a-synuclein were evident. The levels of the Ab-degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-b levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brainderived 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.

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

“…Post-mortem studies of brain tissue from patients with HIV-1-associated dementia or HIV encephalitis have found evidence of microvascular degeneration and BBB breakdown, including reduced pericyte coverage 177 . Vascular insults, including enlarged perivascular spaces 64,151,178 and mineralization of mural cells of deep penetrating blood vessels 171 , have also been found in brain tissue from patients with CTE 64,151,171,178 .…”

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

“…In long-term survivors of TBI, neprilysin accumulates in axons and in the same axonal bulbs as APP and Aβ - indicating that it may be important for the local clearance of TBI-induced Aβ (Chen et al, 2009). Furthermore, levels of neprilysin are reduced in patients with traumatic encephalopathy compared to non-demented controls (Kokjohn et al, 2013). …”

Traumatic brain injury, neuroimaging, and neurodegeneration

“…This observation suggests incubation and interactive effect of the prior injury with time and aging effects. McKee et al (2012) conclude that the association of CTE “… with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein (p. 43).” Dementia pugilistica has been diagnosed in as high as 20% of retired boxers and may have its onset long after the last boxing match (Kokjohn et al, 2013). …”