Journal
NEUROBIOLOGY OF DISEASE
Volume 14, Issue 3, Pages 391-403Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2003.07.006
Keywords
Alzheimer's disease (AD); amyloid precursor protein (APP); cleavage of APP (cAPP); caspase-3; Tau protein
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Funding
- NATIONAL INSTITUTE ON AGING [P01AG000538] Funding Source: NIH RePORTER
- NIA NIH HHS [P01 AG00538] Funding Source: Medline
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The activation of caspase-3 and possibly other caspases during apoptosis may lead to the cleavage of the amyloid precursor protein (APP) and subsequent accumulation of APP cleavage products (cAPP). We examined the association between activated caspase-3 and cAPP in human brain by qualitative and quantitative analysis of in situ immumohistochemistry and Western blots. Frontal cortex and hippocampal tissue from age-matched control and Alzheimer's brains (AD) was used. Both activated caspase-3 and cAPP are increased in AD [Braak and Braak (BB) stage IV-VI] compared to aged control (BB stage 0-1) and transitional (BB stage II-III) cases in the hippocampal and frontal cortex. Caspase-3 activation and the accumulation of APP cleavage fragments appear to either parallel or precede neurofibrillary tangle formation. These findings raise the possibility that the activation of caspase-3 and cleavage of APP may be involved with neuronal degeneration and that pathways characteristic of apoptosis are activated in AD. (C) 2003 Elsevier Inc. All rights reserved.
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