Increasing evidence points to Aβ-containing senile plaques as primary etiological agents in Alzheimer's disease (AD). The mechanism by which these deposits cause neurotoxicity is unresolved, but there are compelling data suggesting that the activated glia found associated with senile plaques contribute to the pathology of AD. These cells appear to release a variety of immunoinflammatory molecules, including complement proteins whose activation products colocalize with senile plaques and dystrophic neurites. Previous studies showed that Aβ can bind and activate complement protein C1q, providing a plausible explanation for the initiation of the complement cascade in AD. Data presented here further define the nature of Aβ-C1q association, revealing key aspects of the C1q domain involved in binding the amyloid peptide. Moreover, we show that it is possible to inhibit Aβ-induced complement activation without affecting the normal immunoglobulin-mediated complement pathway. This indicates that it should be feasible to develop drugs to reduce complement damage in AD without compromising this important immune-defense mechanism throughout the body.