In Situ Immunodetection of Neuronal Caspase-3 Activation in Alzheimer Disease

• Published in: Journal of neuropathology and experimental neurology Vol. 58; no. 9; pp. 1020 - 1026
• Main Authors: SELZNICK, LEE A, HOLTZMAN, DAVID M, HAN, BYUNG HEE, GOKDEN, MURAT, SRINIVASAN, ANU N, JOHNSON, EUGENE M, ROTH, KEVIN A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.09.1999; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Aged; Alzheimer Disease - enzymology; Alzheimer Disease - pathology; Amyloid beta-Peptides - pharmacology; Amyloid beta-Protein Precursor - genetics; Animals; Biological and medical sciences; Brain - enzymology; Brain - pathology; Caspase 3; Caspases - metabolism; Cells, Cultured; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Enzyme Activation; Humans; Immunohistochemistry; Medical sciences; Mice; Mice, Transgenic - genetics; Middle Aged; Mutation; Neurofibrillary Tangles - pathology; Neurology; Neurons - enzymology; Peptide Fragments - pharmacology; Plaque, Amyloid - pathology; Human; Immunohistochemistry; Pathology; Nervous system diseases; Alzheimer disease; In situ; Central nervous system disease; Exploration; Degenerative disease; Cerebral disorder; Apoptosis
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199909000-00012

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 (Aβ deposition in the APPsw transgenic mouse model of AD does not result in caspase- 3 activation despite the ability of Aβ 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.