Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice

Jean Cosme Dodart, Chantal Mathis, Josep Saura, Kelly R. Bales, Steven M. Paul, Arielle Ungerer

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Histological analyses were performed on the brains of APP(V717F) transgenic (Tg) mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the APP(V717F) transgene and independent of amyloid deposition. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)71-85
Number of pages15
JournalNeurobiology of Disease
Volume7
Issue number2
DOIs
StatePublished - Apr 2000

Keywords

  • APP
  • Alzheimer's disease
  • Amyloid precursor protein
  • Computer-assisted image analysis
  • Hippocampus
  • Immunohistochemistry
  • Synaptic density
  • Synaptophysin
  • Transgenic mice

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