Veterans Affairs Health Care System, Iowa City, IA, USA.
Neurochem Res. 2013 Sep;38(9):1777-84. doi: 10.1007/s11064-013-1080-6. Epub 2013 May 29.
Alzheimer's disease (AD) is characterized by the presence of neuropathological lesions containing amyloid plaques (APs) and hyperphosphorylated Tau containing neurofibrillary tangles (NFTs) and is associated with neuroinflammation and neurodegeneration. Entorhinal cortex (Brodmann's area 28) is involved in memory associated functions and is one of the first brain areas targeted to form the neuropathological lesions and also severely affected cortical region in AD. Glia maturation factor (GMF), a central nervous system protein and a proinflammatory molecule is known to be up-regulated in the specific areas of AD brain. Our previous immunohistochemical studies using temporal cortex showed that GMF is expressed in the vicinity of APs and NFTs in AD brains. In the present study, we have analyzed the expression of GMF and its association with APs and NFTs in the entorhinal cortex of AD brains by using immunohistochemistry combined with thioflavin-S fluorescence labeling methods. Results showed that GMF immunoreactive glial cells, glial fibrillary acidic protein labeled reactive astrocytes and ionized calcium binding adaptor molecule-1 labeled activated microglia were increased in the entorhinal cortical layers especially at the sites of 6E10 labeled APs and Tau containing NFTs. In conclusion, increased expression of GMF by the glial cells in the entorhinal cortex region, and the co-localization of GMF with APs and NFTs suggest that GMF may play important proinflammatory roles in the pathogenesis of AD.
阿尔茨海默病(AD)的特征是存在包含淀粉样斑块(APs)的神经病理学病变和含有过度磷酸化 Tau 的神经原纤维缠结(NFTs),并且与神经炎症和神经退行性变有关。内嗅皮层(Brodmann 区 28)参与与记忆相关的功能,是形成神经病理学病变的第一个大脑区域之一,也是 AD 中受严重影响的皮质区域。神经胶质成熟因子(GMF)是一种中枢神经系统蛋白和促炎分子,已知在 AD 大脑的特定区域中上调。我们之前使用颞叶皮层进行的免疫组织化学研究表明,GMF 在 AD 大脑中的 AP 和 NFT 附近表达。在本研究中,我们通过使用免疫组织化学结合硫黄素-S 荧光标记方法分析了 AD 大脑内嗅皮层中 GMF 的表达及其与 AP 和 NFT 的关联。结果表明,GMF 免疫反应性神经胶质细胞、胶质纤维酸性蛋白标记的反应性星形胶质细胞和离子钙结合衔接蛋白-1 标记的活化小胶质细胞在内嗅皮质层中增加,特别是在 6E10 标记的 AP 和 Tau 包含的 NFT 部位。总之,内嗅皮层区域中神经胶质细胞 GMF 的表达增加以及 GMF 与 AP 和 NFT 的共定位表明,GMF 可能在 AD 的发病机制中发挥重要的促炎作用。