In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease.
The mechanism by which cells die in Alzheimer disease (AD) is unknown. Several investigators speculate that much of the cell loss may be due to apoptosis, a highly regulated form of programmed cell death. Caspase-3 is a critical effector of neuronal apoptosis and may be inappropriately activated in AD. To address this possibility, we examined cortical and hippocampal brain sections from AD patients, as well as 2 animal models of AD, for in situ evidence of caspase-3 activation. We report here that senile plaques and neurofibrillary tangles in the AD brain are not associated with caspase-3 activation. Furthermore, amyloid beta (A beta) deposition in the APPsw transgenic mouse model of AD does not result in caspase-3 activation despite the ability of A beta to induce caspase-3 activation and neuronal apoptosis in vitro. AD brain sections do, however, exhibit caspase-3 activation in hippocampal neurons undergoing granulovacuolar degeneration. Our data suggests that caspase-3 does not have a significant role in the widespread neuronal cell death that occurs in AD, but may contribute to the specific loss of hippocampal neurons involved in learning and memory.
Selznick
L A
LA
Department of Pathology, Center for Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Holtzman
D M
DM
Han
B H
BH
Gökden
M
M
Srinivasan
A N
AN
Johnson
E M
EM
Roth
K A
KA
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000201:enzymology*; D010446:Peptide Fragments / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000473:pathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases