Inflammatory mechanisms in neurodegeneration and Alzheimerʹs disease: The role of the complement system

This review discusses key findings indicating potential roles of the complement (C)-system in chronic inflammation in Alzheimerʹs disease (AD) brain. Although there is no means to cure or prevent the disease, recent studies suggest that antiinflammatory drugs may delay the onset of AD dementia. One target of these drugs may be the (C)-system, which is best known for its roles in inflammatory processes in peripheral tissues. However, recent data show C-system expression and regulation in brain cells, and C-system protein deposition in AD plaques. It is still unclear whether C-system activation contributes to neuropathology in the AD brain, as shown in multiple sclerosis (MS). New clinical studies with antiinflammatory agents are now under general consideration by the Alzheimerʹs Disease Cooperative Study program. In this review I outline research directions which address possible C-system contributions to neurodegeneration. Finally, I discuss potential pharmacological interventions designed to control segments of classical inflammatory cascades in which the C-system is highly implicated. These aspects are critical to the understanding of C-mediated responses in normal and pathologic brain.