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01-09-2010 | Original Paper

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

Authors: Wende Li, Yu’e Wu, Fangui Min, Zhuo Li, Jiayuan Huang, Ren Huang

Published in: Metabolic Brain Disease | Issue 3/2010

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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Title: A nonhuman primate model of Alzheimer’s disease generated by intracranial injection of amyloid-beta42 and thiorphan
Authors: Wende Li
Yu’e Wu
Fangui Min
Zhuo Li
Jiayuan Huang
Ren Huang
Publication date: 01-09-2010
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 3/2010
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-010-9207-9

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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