Long-term accumulation of amyloid-β, β-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma

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Abstract

Plaques composed of amyloid β (Aβ) have been found within days following brain trauma in humans, similar to the hallmark plaque pathology of Alzheimer's disease (AD). Here, we evaluated the potential source of this Aβ and long-term mechanisms that could lead to its production. Inertial brain injury was induced in pigs via head rotational acceleration of 110° over 20 ms in the coronal plane. Animals were euthanized at 3 hours, 3 days, 7 days, and 6 months post-injury. Immunohistochemistry and Western blot analyses of the brains were performed using antibodies specific for amyloid precursor protein (APP), Aβ peptides, β-site APP-cleaving enzyme (BACE), presenilin-1 (PS-1), caspase-3, and caspase-mediated cleavage of APP (CCA). Substantial co-accumulation for all of these factors was found in swollen axons at all time points up to 6 months following injury. Western blot analysis of injured brains confirmed a substantial increase in the protein levels of these factors, particularly in the white matter. These data suggest that impaired axonal transport due to trauma induces long-term pathological co-accumulation of APP with BACE, PS-1, and activated caspase. The abnormal concentration of these factors may lead to APP proteolysis and Aβ formation within the axonal membrane compartment.

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APA

Chen, X. H., Siman, R., Iwata, A., Meaney, D. F., Trojanowski, J. Q., & Smith, D. H. (2004). Long-term accumulation of amyloid-β, β-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. American Journal of Pathology, 165(2), 357–371. https://doi.org/10.1016/S0002-9440(10)63303-2

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