Complement in Alzheimer's disease: opportunities for modulating protective and pathogenic events

The complement system is a critical element of the innate immune system recognizing and killing, or targeting for destruction, otherwise pathogenic organisms. In addition to triggering the generation of a membranolytic complex, complement proteins interact with cell surface receptors to promote a local inflammatory response that contributes to the protection and healing of the host. Compelling evidence has been reported that in Alzheimer's Disease complement activation occurs in the brain, and that this contributes to the development of a local inflammatory state that is correlated with cognitive dysfunction. However, recent data suggest that at least some of the complement components have the ability to contribute to neuroprotective pathways. Thus, it is the balance of these seemingly competing events that influences the ultimate state of neuronal function. Knowledge of the unique molecular interactions that occur in the development of Alzheimer's Disease, the functional consequences of those interactions, and the proportional contribution of each element to this disorder, should facilitate the design of effective therapeutic strategies for this disease.