Yasojima K, Schwab C, McGeer E G, McGeer P L
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.
Am J Pathol. 1999 Mar;154(3):927-36. doi: 10.1016/S0002-9440(10)65340-0.
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.
我们运用逆转录聚合酶链反应和蛋白质印迹技术，来测定与非阿尔茨海默病（AD）脑相比，AD脑内补体mRNA及其蛋白质产物的水平。在所研究的脑的11个区域中检测到了C1q、C1r、C1s、C2、C3、C4、C5、C6、C7、C8和C9的mRNA。AD脑的病变区域中mRNA水平显著上调。在内嗅皮质、海马体和颞中回，这些区域有大量的斑块和缠结堆积，C1q mRNA比对照水平增加了11至80倍，C9 mRNA增加了10至27倍。这些水平显著高于同一病例肝脏中的水平。对AD海马体进行的蛋白质印迹分析证实了所有天然补体蛋白及其激活产物C4d、C3d和膜攻击复合物的存在。这些数据表明，AD脑的病变区域产生了高水平的补体，经典补体途径持续发生完全激活，并且这种激活可能对AD病理有显著影响。
