Abortive apoptosis in Alzheimer's disease
1Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Acta Neuropathologica
|May 18, 2001
Summary
Alzheimer's disease (AD) neurons initiate apoptosis but avoid caspase-dependent death. This "abortosis" may allow neuronal survival despite amyloid-beta pathology.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Neuronal death in Alzheimer's disease (AD) is often linked to apoptosis.
- Hallmarks of terminal apoptosis are absent in AD, suggesting an atypical cell death process.
Purpose of the Study:
- To investigate the role of caspases in Alzheimer's disease-related neuronal death.
- To understand the mechanism of apoptotic signal propagation in AD.
Main Methods:
- Localization of caspases (upstream and downstream) in pathological lesions of AD.
- Analysis of caspase activity in relation to amyloid-beta and presenilin pathology.
Main Results:
- Upstream caspases (8 and 9) are present in AD intraneuronal pathology.
- Downstream caspases (3, 6, and 7) are at control levels, indicating a lack of signal amplification.
- Caspase 6 localizes to amyloid-beta deposits, suggesting a role in processing amyloid-beta protein precursor (AβPP).
Conclusions:
- Alzheimer's disease exhibits a novel phenomenon of "abortive apoptosis" or "abortosis."
- Initiation of apoptosis occurs, but it does not proceed to caspase-dependent cell death.
- This abortosis may be a mechanism for neuronal survival in AD, despite the presence of amyloid-beta pathology.
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