APP(Sw) transgenic mice develop age-related Aβ deposits and neuropil abnormalities, but no neuronal loss in CA1

Michael C. Irizarry, Megan McNamara, Kerri Fedorchak, Karen Hsiao, Bradley T. Hyman

Research output: Contribution to journalArticlepeer-review

554 Scopus citations

Abstract

The recent availability of transgenic mouse models of Alzheimer disease has allowed direct in vivo assessment of the molecular and neuropathological effects of cerebral amyloid deposition. We examined 16-month-old Tg(HuAPP695. K670N-M671L)2576 mice expressing human APP K670N-M671L (APP(Sw)), which have amyloid deposition and behavioral deficits by 11 months of age. Transgene expression is predominantly neuronal, and results in amyloid deposits, comparable to human senile plaques, at terminal zones of transgene positive neurons in cortical and limbic regions. Amyloid deposits were associated with prominent gliosis and neuritic dystrophy, without neuronal loss in CA1, loss of synaptophysin immunoreactivity in the hippocampal dentate gyrus, or loss of messenger RNA for neuronal synaptic, cytoskeletal, or metabolic proteins. We conclude that Aβ is not acutely neurotoxic, but can disrupt neuronal processes and provoke an inflammatory response.

Original languageEnglish (US)
Pages (from-to)965-973
Number of pages9
JournalJournal of neuropathology and experimental neurology
Volume56
Issue number9
DOIs
StatePublished - Sep 1997

Keywords

  • Alzheimer disease
  • Amyloid precursor protein
  • Amyloid β protein
  • Hippocampus
  • Synaptophysin
  • Transgenic models
  • mRNA

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