...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Current Alzheimer Research >Amyloid Deposition and Inflammation in APPswe/PS1dE9 Mouse Model of Alzheimer's Disease
【24h】

Amyloid Deposition and Inflammation in APPswe/PS1dE9 Mouse Model of Alzheimer's Disease

机译：阿尔茨海默氏病APPswe / PS1dE9小鼠模型中的淀粉样蛋白沉积和炎症

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles associated with chronic inflammation. APPswe/PS1dE9 is an AD mouse model bearing mutant transgenes of amyloid precursor protein and presenilin-1. Amyloid deposition is present in this mouse model at early stage of life. However, the progression of inflammation and its relationship with amyloid deposition have not been characterized. Here we showed that amyloid plaques were present at 4 months of age and increased with age. CD11b-positive microglia clusters appeared in hippocampus and neocortex at 4 months of age and increased with age. Clustered glial fibrillary acidic protein (GFAP)-positive astrocytes were observed in hippocampus and cortex after 6 months of age and increased with age. Double staining with CD11b/GFAP antibody and thioflavin S showed clustered microglia and astrocytes were in close association with amyloid plaques. Expression of TNF-α was detected at 8 months of age, while IL-1β, IL-6 and MCP-1 at 10 months. These cytokines increased with age. Double immunostaining of cell specific marker and cytokine indicated TNF-α, IL-1β, IL-6 and MCP-1 were expressed by activated microglia and a small part of activated astrocytes. MCP-1 was also expressed by neurons, which support recent finding that MCP-1 expression was increased in neurons of AD patient. These results demonstrate amyloid plaques and its associated inflammatory response developed at early stage of life and progressively increased with age, both activated glia and neurons are involved in chronic inflammation in AD. APPswe/PS1dE9 model provides a mean for studying the mechanisms and novel therapeutics for AD.
机译：阿尔茨海默氏病（AD）的特征是与慢性炎症相关的淀粉样斑块和神经原纤维缠结。 APPswe / PS1dE9是带有淀粉样蛋白前体蛋白和presenilin-1突变转基因的AD小鼠模型。淀粉样蛋白沉积存在于生命早期的该小鼠模型中。然而，炎症的进程及其与淀粉样蛋白沉积的关系尚未被表征。在这里，我们显示淀粉样蛋白斑块存在于4个月大时，并随年龄增长而增加。 CD11b阳性小胶质细胞簇在4个月大时出现在海马和新皮层中，并随年龄增加而增加。 6个月大后，海马和皮质中观察到成簇的胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞，并随年龄增加而增加。用CD11b / GFAP抗体和硫代黄素S双重染色显示成簇的小胶质细胞和星形胶质细胞与淀粉样斑块密切相关。在8个月大时检测到TNF-α的表达，而在10个月大时检测到IL-1β，IL-6和MCP-1的表达。这些细胞因子随年龄增加。细胞特异性标记物和细胞因子的双重免疫染色表明，TNF-α，IL-1β，IL-6和MCP-1由活化的小胶质细胞和一小部分活化的星形胶质细胞表达。 MCP-1也由神经元表达，这支持了最近发现AD患者神经元中MCP-1表达增加的发现。这些结果表明，淀粉样蛋白斑块及其相关的炎症反应在生命的早期阶段发展，并随着年龄的增长而逐渐增加，活化的神经胶质细胞和神经元均参与AD的慢性炎症。 APPswe / PS1dE9模型为研究AD的机制和新疗法提供了一种手段。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号