Caspase cleavage of the amyloid precursor protein is prevented after overexpression of bcl-2 in a triple transgenic mouse model of Alzheimer's disease.
A recent study demonstrated the lack of beta-amyloid (Abeta) 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 Abeta 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.
Kumasaka
Debra K
DK
Department of Biology, Boise State University, Boise, Idaho, 83725.
Galvan
Veronica
V
Head
Elizabeth
E
Rohn
Troy T
TT
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