IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
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,

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).

Key words: Amyloid precursor protein, beta-amyloid, caspase; mouse model, neurofibrillary tangles, plaques; tau; bcl-2; apoptosis

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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
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