Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Huang Huang, Sipei Nie, Min Cao, Charles Marshall, Junying Gao, Na Xiao, Gang Hu, Ming Xiao

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer’s disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular Aβ. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.

Original languageEnglish
Pages (from-to)303-322
Number of pages20
JournalAge
Volume38
Issue number4
DOIs
StatePublished - Aug 1 2016

Bibliographical note

Publisher Copyright:
© 2016, American Aging Association.

Keywords

  • APP/PS1 mice
  • Aged
  • Alzheimer’s disease
  • Hippocampal atrophy
  • Noncognitive abnormalities
  • β-amyloid

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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