Inhibition of C1q-β-amyloid binding protects hippocampal cells against complement mediated toxicity

Activation of complement by β-amyloid (Aβ) contributes to the pathology of Alzheimer's disease (AD). Here, we show that C1-Inhibitor (C1-Inh) protects cultured rat hippocampal cells against β-amyloid induced complement lysis indicating a classical pathway-mediated activation mechanism. We report on screening of compound libraries to identify compounds that inhibit C1q binding to β-amyloid. Characterization of these compounds revealed that C1q possessed distinct binding sites for β-amyloid and antibodies. One selected compound protected cultured hippocampal cells against complement-dependent β-amyloid toxicity. These results provide evidence that complement has the potential to damage hippocampal cells, and C1q is a relevant target to suspend this deleterious mechanism in Alzheimer's disease.