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A nonhuman primate model of Alzheimer’s disease generated by intracranial injection of amyloid-beta42 and thiorphan

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathological changes, including the deposition of amyloid-beta (Aβ) peptide. Aged monkeys have proven to be invaluable in the study of AD, as their brains naturally develop amyloid plaques similar to those in AD brains. However, spontaneous development of AD-like pathologies in aged monkeys is time-consuming, often taking several years. Here, we created an experimentally induced AD model in middle-aged (16-17 years) rhesus monkeys by intracranial injection of Aβ42 and thiorphan, an inhibitor of neprilysin that is responsible for Aβ clearance. The working memory capacity of the monkeys in a delayed-response task was little affected following the delivery of Aβ42 and thiorphan. However, the administration of Aβ42 and thiorphan resulted in a significant intracellular accumulation of Aβ in the neurons of the basal ganglia, the cortex, and the hippocampus, accompanied by neuronal atrophy and loss. Moreover, immunohistochemistry revealed a degeneration of choline acetyltransferase-positive cholinergic neurons and an increase of glial fibrillary acidic protein-positive astrocytes. In conclusion, our data demonstrate a primate model of AD generated by combined infusion of Aβ42 and thiorphan, which duplicates a subset of neuropathological changes in AD brains, thereby having implications in the elucidation of this disease.

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Acknowledgements

This work was supported by Science and Technology Planning Project of Guangdong Province, China (2006B36004015 and 2009B060300017) and by Natural Science Foundation of Guangdong Province, China (010086 and 06023013).

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Authors and Affiliations

  1. Key Laboratory of Natural Drug Research and Development of Guangdong, Department of Pharmacology, Guangdong Medical College, Zhanjiang, 524023, China

    Wende Li & Fangui Min

  2. Guangdong Laboratory Animals Monitoring Institute, Guangzhou, 510260, China

    Yu’e Wu & Ren Huang

  3. Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524023, China

    Zhuo Li

  4. The First Clinical Institute of Guangdong Medical College, Zhanjiang, 524023, China

    Jiayuan Huang

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  1. Wende Li
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  2. Yu’e Wu
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  3. Fangui Min
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  4. Zhuo Li
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  5. Jiayuan Huang
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  6. Ren Huang
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Correspondence to Ren Huang.

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Li, W., Wu, Y., Min, F. et al. A nonhuman primate model of Alzheimer’s disease generated by intracranial injection of amyloid-beta42 and thiorphan. Metab Brain Dis 25, 277–284 (2010). https://doi.org/10.1007/s11011-010-9207-9

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  • DOI: https://doi.org/10.1007/s11011-010-9207-9

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