Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: relationship to formic acid extractable abeta42 levels.
Recent studies support the hypothesis that Alzheimer disease (AD)-associated amyloid-beta protein (Abeta) 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, Abeta40 or Abeta42 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 Abeta42 levels. Our results suggest that the transcriptional activation of key components of the apoptotic cascade correlates with accumulation of Abeta 42. Thus, a principal caspase pathway from caspase-8 to caspase-3 and/or 7 may contribute to neuron loss in AD brain.
Matsui
Toshifumi
T
Alzheimer Research Unit, Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Ramasamy
Karunya
K
Ingelsson
Martin
M
Fukumoto
Hiroaki
H
Conrad
Cintia
C
Frosch
Matthew P
MP
Irizarry
Michael C
MC
Yuan
Junying
J
Hyman
Bradley T
BT
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016022:Case-Control Studies; D020169:Caspases / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005561:Formates / Q000737:chemistry; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000145:classification / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D016229:Amyloid beta-Peptides; D005561:Formates; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); C030544:formic acid; D020169:Caspases