Int J Physiol Pathophysiol Pharmacol 2009;1(1):48-56.
Original Article Caspase cleavage of the amyloid precursor protein is prevented after overexpression of bcl-2 in a triple transgenic mouse model of Alzheimer’s disease
Debra K. Kumasaka, Veronica Galvan, Elizabeth Head, Troy T. Rohn
Department of Biology, Science/Nursing Building, Room 228, Boise State University, Boise, Idaho, 83725; 2Buck Institute for Age Research Novato, CA, 94945; 3Institute for Brain Aging and Dementia, Department of Neurology, University of California, Irvine, CA, 92697
Received January 12, 2009 accepted January, 2009; available online January, 2009
Abstract: A recent study demonstrated the lack of beta-amyloid (Aβ) plaque formation and accumulation of the amyloid precursor protein (APP) in a triple transgenic mouse model of Alzheimer’s disease (3xTg-AD) following overexpression of the anti-apoptotic protein, Bcl-2 (Rohn et al., J. Neurosci. 28: 3051-9, 2008). The supposition from that study was the accumulation of APP resulted from a decrease in caspase-mediated processing of APP. To determine a direct role for the caspase-cleavage of APP in 3xTg-AD mice, we designed a site-directed caspase-cleavage antibody to APP and demonstrated it is a specific marker for caspase-cleaved APP. Application of this antibody revealed neuronal staining in the hippocampus and subiculum of 3xTg-AD mice. These results were confirmed utilizing a similar site-directed antibody to caspase-cleaved APP (APPneo). The caspase cleavage of APP as well as the formation of extracellular Aβ plaques was prevented in 3xTg-AD animals overexpressing Bcl-2. These results provide further support that caspases play a proximal role in promoting the pathology associated with AD. (IJPPP901001).
Address all correspondence to: Troy T. Rohn, PhD Department of Biology Science/Nursing Building, Room 228 Boise State University Boise, Idaho, 83725 Phone number: (208)-426-2396 Fax number: (208-426-4267 Email address: firstname.lastname@example.org