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Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice.
Age (Dordr) 2016; 38(4):303-322A

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.

Authors+Show Affiliations

Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China. Department of Neurology, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China.Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China.Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China. Department of Rehabilitation Sciences, University of Kentucky Center of Excellence in Rural Health, Hazard, KY, 41701, USA.Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China.Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China.Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China.Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China. mingx@njmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27439903

Citation

Huang, Huang, et al. "Characterization of AD-like Phenotype in Aged APPSwe/PS1dE9 Mice." Age (Dordrecht, Netherlands), vol. 38, no. 4, 2016, pp. 303-322.
Huang H, Nie S, Cao M, et al. Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice. Age (Dordr). 2016;38(4):303-322.
Huang, H., Nie, S., Cao, M., Marshall, C., Gao, J., Xiao, N., ... Xiao, M. (2016). Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice. Age (Dordrecht, Netherlands), 38(4), pp. 303-322. doi:10.1007/s11357-016-9929-7.
Huang H, et al. Characterization of AD-like Phenotype in Aged APPSwe/PS1dE9 Mice. Age (Dordr). 2016;38(4):303-322. PubMed PMID: 27439903.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice. AU - Huang,Huang, AU - Nie,Sipei, AU - Cao,Min, AU - Marshall,Charles, AU - Gao,Junying, AU - Xiao,Na, AU - Hu,Gang, AU - Xiao,Ming, Y1 - 2016/07/21/ PY - 2016/04/28/received PY - 2016/07/12/accepted PY - 2016/7/22/pubmed PY - 2017/12/15/medline PY - 2016/7/22/entrez KW - APP/PS1 mice KW - Aged KW - Alzheimer’s disease KW - Hippocampal atrophy KW - Noncognitive abnormalities KW - β-amyloid SP - 303 EP - 322 JF - Age (Dordrecht, Netherlands) JO - Age (Dordr) VL - 38 IS - 4 N2 - 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. SN - 1574-4647 UR - https://www.unboundmedicine.com/medline/citation/27439903/Characterization_of_AD_like_phenotype_in_aged_APPSwe/PS1dE9_mice_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27439903/ DB - PRIME DP - Unbound Medicine ER -