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

作者：Li, Wende; Wu, Yu'e; Min, Fangui; Li, Zhuo; Huang, Jiayuan; Huang, Ren^*

来源：Metabolic Brain Disease, 2010, 25(3): 277-284.

DOI：10.1007/s11011-010-9207-9

• Alzheimer's disease (AD)
• Thiorphan
• Amyloid-beta (A beta) peptide
• Primate model
• Choline acetyltransferase (ChAT)
• Glial fibrillary acidic protein (GFAP)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathological changes, including the deposition of amyloid-beta (A beta) 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 A beta 42 and thiorphan, an inhibitor of neprilysin that is responsible for A beta clearance. The working memory capacity of the monkeys in a delayed-response task was little affected following the delivery of A beta 42 and thiorphan. However, the administration of A beta 42 and thiorphan resulted in a significant intracellular accumulation of A beta 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 A beta 42 and thiorphan, which duplicates a subset of neuropathological changes in AD brains, thereby having implications in the elucidation of this disease.

• 出版日期2010-9
• 单位广东医科大学