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


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.

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This work was supported by the grants from the National Natural Science Foundation of China (30971020 and 30973517) and the Natural Science Foundation of Jiangsu Educational Department (09KJA310003).

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Correspondence to Ming Xiao.

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Huang, H., Nie, S., Cao, M. et al. Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice. AGE 38, 303–322 (2016). https://doi.org/10.1007/s11357-016-9929-7

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