Detection of complement alternative pathway mRNA and proteins in the Alzheimer's disease brain

Previous research on complement activation in the Alzheimer's disease (AD) brain has focused almost exclusively on the classical complement pathway. The alternative pathway represents another important arm for complement activation, converging with the classical cascade at the C5 cleavage step. Here, we show that mRNA for a critical alternative pathway component, factor B, is present in AD frontal cortex and that the factor D cleaved split products of factor B, Bb and Ba, are significantly increased, indicating alternative pathway activation. By contrast, the two major inhibitors of alternative pathway activation, factor H and factor I, are present at the level of mRNA and protein but are not significantly upregulated. Immunohistochemical analysis reveals significant positive staining in AD sections for all three components. Taken together with previous reports demonstrating alternative pathway activation by amyloid beta peptide, these findings suggest that conditions conducive to chronic alternative pathway activation may exist in the AD brain.