Up-regulated production and activation of the complement system in Alzheimer's disease brain

We used reverse transcriptase-polymerase chain reaction and Western blottin g techniques to measure the levels of complement mRNAs and their protein pr oducts 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 u p-regulated In affected areas of AD brain. In the entorhinal cortex, hippoc ampus, 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 liv ers of the same cases. Western blot analysis of AD hippocampus established the presence of all of the native complement proteins as well as their acti vation products C4d, C3d, and the membrane attack complex. These data indic ate that high levels of complement are being produced In affected areas of AD brain, that full activation of the classical complement pathway Is conti nuously taking place, and that this activation may be contributing signific antly to AD pathology.