Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation.
Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation.
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DOI：
10.1038/s41598-017-17999-3
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发表时间：
2017-12-19
影响因子：
4.6
通讯作者：
Nakabeppu Y
中科院分区：
文献类型：
--
作者：
Castillo E;Leon J;Mazzei G;Abolhassani N;Haruyama N;Saito T;Saido T;Hokama M;Iwaki T;Ohara T;Ninomiya T;Kiyohara Y;Sakumi K;LaFerla FM;Nakabeppu Y
阿尔茨海默病（AD）是最常见的痴呆形式，其特征是β淀粉样蛋白（Aβ）和神经原纤维缠结的积累。氧化应激和炎症被认为在AD的发生和发展中起重要作用。然而，这些事件在多大程度上导致Aβ病变仍不清楚。我们对AD患者大脑和App NL-G-F/NL-G-F和3xTg-AD-H小鼠模型进行了种间比较基因表达谱分析。App NL-G-F/NL-G-F和人类AD皮质中常见的基因改变与炎症反应或免疫性疾病相关。其中，AD相关基因（C4a/C4b、Cd74、Ctss、Gfap、Nfe2l2、Phyhd1、S100b、Tf、Tgfbr2、Vim）在App NL-G-F/NL-G-F皮层的表达随着Aβ淀粉样变性的进展而增加，而在3xTg-AD-H和人类AD皮层中常见的基因改变与神经系统疾病相关。App NL-G-F/NL-G-F皮层也有基因表达改变（Abi3、Apoe、Bin2、Cd33、Ctsc、Dock2、Fcer1g、Frmd6、Hck、Inpp5D、Ly86、Plcg2、Trem2、Tyrobp），这些基因被全基因组关联研究定义为阿尔茨海默病的危险因素，或被确定为晚发性阿尔茨海默病的遗传节点。这些结果表明皮质β淀粉样变与神经炎症反应之间存在很强的相关性，并提供了对AD发展中性别影响的更好理解。
Alzheimer’s disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the Aβ pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App NL-G-F/NL-G-F and 3xTg-AD-H mouse models. Genes commonly altered in App NL-G-F/NL-G-F and human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App NL-G-F/NL-G-F cortex as Aβ amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. The App NL-G-F/NL-G-F cortex also had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2, Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aβ amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD.
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