In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease

Lee A. Selznick, David M. Holtzman, Byung Hee Han, Murat Gökden, Anu N. Srinivasan, Eugene M. Johnson, Kevin A. Roth

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1020-1026
Number of pages7
JournalJournal of neuropathology and experimental neurology
Volume58
Issue number9
DOIs
StatePublished - Sep 1999

Keywords

  • Alzheimer disease
  • Amyloid beta
  • Apoptosis
  • Autophagy
  • Caspase- 3
  • Granulovacuolar degeneration

Fingerprint

Dive into the research topics of 'In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease'. Together they form a unique fingerprint.

Cite this