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J Neuropathol Exp Neurol. 2002 Dec;61(12):1056-68.

Long-term accumulation of amyloid-beta in axons following brain trauma without persistent upregulation of amyloid precursor protein genes.

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Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6316, USA.


Brain trauma has been shown to be a risk factor for developing Alzheimer disease (AD), and AD-like plaques containing amyloid-beta (Abeta) peptides have been found in the brain shortly following trauma. Here, we evaluated the effects of brain trauma on the accumulation of Abeta and expression of amyloid precursor protein (APP) genes (APP695 and APP751/ 770) over 1 yr in a non-transgenic rodent model. Anesthetized male Sprague-Dawley rats were subjected to parasagittal fluid percussion brain injury of moderate severity (2.5-2.9 atm) or sham treatment and their brains were evaluated at 2, 4, 7, 14 days, and 1, 2, 6, 12 months following injury. Immunohistochemical analysis detected only weak Abeta staining by 2 wk following injury. However, by 1 month to 1 yr following injury, strong immunoreactivity for Abeta was found in damaged axons throughout the thalamus and white matter. Western blot analysis confirmed the accumulation of Abeta peptides in tissue from injured brains. Although in situ hybridization demonstrated an increased gene expression of APP751/770 surrounding the cortical lesion at 2 to 7 days following injury, this expression returned to baseline levels at all subsequent time points and no increase in the expression of APP695 was detected at any time point. These results demonstrate that long-termAbeta accumulation in damaged axons can be induced in a non-transgenic rodent model of brain trauma. Surprisingly, the extent of this Abeta production appeared to be dependent on the maturity of the injury, but uncoupled from the gene expression of APP. Together, these data suggest a mechanism that may contribute to long-term neurodegeneration following brain trauma.

[Indexed for MEDLINE]

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