Neuronal DNA damage correlates with overexpression of interleukin-1β converting enzyme in APPV717F mice

J. G. Sheng, R. E. Mrak, R. A. Jones, M. M. Brewer, X. Q. Zhou, J. McGinness, S. Woodward, K. Bales, S. M. Paul, B. Cordell, W. S.T. Griffin

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Transgenic APPV717F mice, homozygous for a human minigene encoding the V717F familial Alzheimer's disease mutation, develop Aβ plaques similar to those seen in Alzheimer patients and show evidence of neuronal cell drop out in CA2-3 regions of the hippocampus at 8 months of age and older. Interleukin-1 (IL-1)β (IL-1β) converting enzyme (ICE) is a cysteine protease (caspase-1) that processes inactive (33 kDa) pro-IL-1β to the active (17 kDa) inflammatory cytokine. We used immunohistochemistry, RT-PCR, and DNA cleavage (TUNEL) analysis to show progressive, age-associated increases in ICE mRNA levels, in the numbers of ICE-immunoreactive glia, and in the numbers of neurons showing evidence of DNA damage in APPV717F mice that commenced months prior to the appearance of Aβ plaques. Moreover, there were significant correlations between these parameters over an age range of 1-17 months. These findings are consistent with the idea that increases in ICE activity and expression contribute to neuronal injury in Alzheimer's disease.

Original languageEnglish
Pages (from-to)895-902
Number of pages8
JournalNeurobiology of Aging
Volume22
Issue number6
DOIs
StatePublished - Dec 1 2001
Externally publishedYes

Keywords

  • APPV717F transgenic mice
  • DNA degradation
  • ICE
  • IL-1β converting enzyme
  • RT-PCR
  • TUNEL
  • Transgenic mice
  • β-Amyloid

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    Sheng, J. G., Mrak, R. E., Jones, R. A., Brewer, M. M., Zhou, X. Q., McGinness, J., Woodward, S., Bales, K., Paul, S. M., Cordell, B., & Griffin, W. S. T. (2001). Neuronal DNA damage correlates with overexpression of interleukin-1β converting enzyme in APPV717F mice. Neurobiology of Aging, 22(6), 895-902. https://doi.org/10.1016/S0197-4580(01)00298-6