Up-regulated production and activation of the complement system in Alzheimer's disease brain
Up-regulated production and activation of the complement system in Alzheimer's disease brain
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DOI：
10.1016/s0002-9440(10)65340-0
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发表时间：
1999-03-01
影响因子：
6
通讯作者：
McGeer, PL
中科院分区：
文献类型：
--
作者：
Yasojima, K;Schwab, C;McGeer, PL
我们使用逆转录聚合酶链反应和蛋白质印迹技术来测量阿尔茨海默病（AD）脑与非AD脑相比，补体mRNA及其蛋白产物的水平。在研究的11个脑区中检测到C1q、C1r、C1s、C2、C3、C4、C5、C6、C7、C8和C9的mRNA。在AD脑内病变区，mRNA水平明显上调。在内嗅皮层、海马和颞中回中，斑块和缠结密集堆积，C1q mRNA比对照水平增加11至80倍，C9 mRNA增加10至27倍。这些水平大大高于相同病例的肝脏。AD海马的Western印迹分析确定了所有天然补体蛋白以及它们的活化产物C4d、C3d和膜攻击复合物的存在。这些数据表明，在AD脑的受影响区域中产生高水平的补体，经典补体途径的完全激活持续发生，并且这种激活可能对AD病理学有显著贡献。
We used reverse transcriptase-polymerase chain reaction and Western blotting techniques to measure the levels of complement mRNAs and their protein products in Alzheimer's disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain that were investigated. The mRNA levels were markedly up-regulated In affected areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus, which had dense accumulations of plaques and tangles, C1q mRNA was increased 11- to 80-fold over control levels, and C9 mRNA 10- to 27-fold. These levels were substantially higher than in the livers of the same cases. Western blot analysis of AD hippocampus established the presence of all of the native complement proteins as well as their activation products C4d, C3d, and the membrane attack complex. These data indicate that high levels of complement are being produced In affected areas of AD brain, that full activation of the classical complement pathway Is continuously taking place, and that this activation may be contributing significantly to AD pathology.