This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, X.-H. Articles by Smith, D. H. Search for Related Content PubMed PubMed Citation Articles by Chen, X.-H. Articles by Smith, D. H.

(American Journal of Pathology. 2004;165:357-371.)
© 2004 American Society for Investigative Pathology

Long-Term Accumulation of Amyloid-ß, ß-Secretase, Presenilin-1, and Caspase-3 in Damaged Axons Following Brain Trauma

Xiao-Han Chen^*, Robert Siman, Akira Iwata^*, David F. Meaney, John Q. Trojanowski and Douglas H. Smith^*

From the Departments of Neurosurgery,^* Pharmacology, Bioengineering, and Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Plaques composed of amyloid ß (Aß) 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 Aß 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), Aß peptides, ß-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 Aß formation within the axonal membrane compartment.

This article has been cited by other articles:

				M. T. Fodero-Tavoletti, C. C. Rowe, C. A. McLean, L. Leone, Q.-X. Li, C. L. Masters, R. Cappai, and V. L. Villemagne Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias J. Nucl. Med., February 1, 2009; 50(2): 198 - 204. [Abstract] [Full Text] [PDF]

				J. Zhao, Y. Fu, M. Yasvoina, P. Shao, B. Hitt, T. O'Connor, S. Logan, E. Maus, M. Citron, R. Berry, et al. {beta}-Site Amyloid Precursor Protein Cleaving Enzyme 1 Levels Become Elevated in Neurons around Amyloid Plaques: Implications for Alzheimer's Disease Pathogenesis J. Neurosci., April 4, 2007; 27(14): 3639 - 3649. [Abstract] [Full Text] [PDF]

				G. B. Stokin, C. Lillo, T. L. Falzone, R. G. Brusch, E. Rockenstein, S. L. Mount, R. Raman, P. Davies, E. Masliah, D. S. Williams, et al. Axonopathy and Transport Deficits Early in the Pathogenesis of Alzheimer's Disease Science, February 25, 2005; 307(5713): 1282 - 1288. [Abstract] [Full Text] [PDF]