Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 65, Issue 5, Pages 508-515Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.jnen.0000229238.05748.12
Keywords
Alzheimer disease; amyloid beta protein; apoptosis; caspase
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Funding
- NIA NIH HHS [P50AG 05134, AG08487] Funding Source: Medline
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Recent studies support the hypothesis that Alzheimer disease (AD)-associated amyloid-beta protein (AP) may induce apoptosis mediated by a caspase cascade. To assess whether mRNA levels of caspase-3, 7, 8 and 9 change in AD brain, and whether these changes correlate with neurofibrillary tangles, A beta(40) or A beta(42) protein levels or senile plaques, 25 AD and 21 non-demented control brains were examined. Elevated mRNA levels of caspases-7 and 8 measured by a quantitative PCR method were observed in the AD temporal neocortex as compared to the control brains. No significant differences were noticed in levels of caspases-3 or 9 between AD and control brains. Multiple regression analysis demonstrated that, within subjects, the mRNA levels of caspase-8 strongly correlated with both caspse-3 and caspase-7 independently of postmortem interval. Further, there was a strong positive correlation of caspase-8 levels with formic acid extractable A beta(42) levels. Our results suggest that the transcriptional activation of key components of the apoptotic cascade correlates with accumulation of A beta(42). Thus, a principal caspase pathway from caspase-8 to caspase-3 and/or 7 may contribute to neuron loss in AD brain.
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