The complement cascade in Alzheimer's disease.

Abstract

Numerous studies show that activated glial cells release increased amounts of several molecules that might contribute to the pathology of Alzheimer's disease (AD), including complement proteins. The complement proteins are particularly noteworthy because of their well-documented ability to induce inflammation, destroy foreign cells and, in certain circumstances, inflict damage to host tissue. There appears to be a general consensus that the early components of the classical complement pathway are found associated with senile plaques in AD brain; of some dispute is whether the later complement products are truly found in AD brain. An unequivocal demonstration of the terminal complement activation products in AD brain is important in strengthening the hypothesis that these products contribute to disease pathology. To date, it has been difficult to determine the extent to which complement activation contributes to the neuropathology of AD. Given the potential detrimental consequences of complement activation in AD brain, there is compelling reason to identify potential therapeutic agents that might attenuate complement activity in this disease. Based on the evidence that Abeta is a likely activator of complement in AD, and on the understanding of the nature of Abeta-C1q binding, it is possible that drugs might be developed that will slow complement activity in the AD brain without compromising this defense mechanism throughout the rest of the body.