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丁酰胆碱酯酶与阿尔茨海默病转基因 APPSWE/PSEN1dE9 小鼠模型中的β-淀粉样斑块有关。

Butyrylcholinesterase is associated with β-amyloid plaques in the transgenic APPSWE/PSEN1dE9 mouse model of Alzheimer disease.

机构信息

Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

J Neuropathol Exp Neurol. 2012 Jan;71(1):2-14. doi: 10.1097/NEN.0b013e31823cc7a6.

Abstract

Histochemical analysis of Alzheimer disease (AD) brain tissues indicates that butyrylcholinesterase (BuChE) is present in β-amyloid (Aβ) plaques. The role of BuChE in AD pathology is unknown, but an animal model developing similar BuChE-associated Aβ plaques could provide insights. The APPSWE/PSEN1dE9 transgenic mouse (ADTg), which develops Aβ plaques, was examined to determine if BuChE associates with these plaques, as in AD. We found that in mature ADTg mice, BuChE activity associated with Aβ plaques. The Aβ-, thioflavin-S- and BuChE-positive plaques mainly accumulated in the olfactory structures, cerebral cortex, hippocampal formation, amygdala, and cerebellum. No plaques were stained for acetylcholinesterase activity. The distribution and abundance of plaque staining in ADTg closely resembled many aspects of plaque staining in AD. Butyrylcholinesterase staining consistently showed fewer plaques than were detected with Aβ immunostaining but a greater number of plaques than were visualized with thioflavin-S. Double-labeling experiments demonstrated that all BuChE-positive plaques were Aβ positive, whereas only some BuChE-positive plaques were thioflavin-S positive. These observations suggest that BuChE is associated with a subpopulation of Aβ plaques and may play a role in AD plaque maturation. A further study of this animal model could clarify the role of BuChE in AD pathology.

摘要

阿尔茨海默病(AD)脑组织的组织化学分析表明,丁酰胆碱酯酶(BuChE)存在于β-淀粉样蛋白(Aβ)斑块中。BuChE 在 AD 病理学中的作用尚不清楚,但开发出具有类似 BuChE 相关 Aβ斑块的动物模型可能会提供一些见解。APPSWE/PSEN1dE9 转基因小鼠(ADTg)会形成 Aβ斑块,我们对其进行了研究,以确定 BuChE 是否与这些斑块有关,就像在 AD 中一样。我们发现,在成熟的 ATDTg 小鼠中,BuChE 活性与 Aβ斑块有关。Aβ、硫黄素-S 和 BuChE 阳性斑块主要积聚在嗅觉结构、大脑皮层、海马结构、杏仁核和小脑。乙酰胆碱酯酶活性未染色的斑块。ADTg 中的斑块染色分布和丰度与 AD 中斑块染色的许多方面非常相似。BuChE 染色显示的斑块数量始终比 Aβ免疫染色检测到的斑块少,但比硫黄素-S 检测到的斑块多。双标记实验表明,所有 BuChE 阳性斑块均为 Aβ 阳性,而只有一些 BuChE 阳性斑块为硫黄素-S 阳性。这些观察结果表明,BuChE 与 Aβ 斑块的一个亚群有关,并且可能在 AD 斑块成熟中发挥作用。对这种动物模型的进一步研究可以阐明 BuChE 在 AD 病理学中的作用。

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