Association of factor H of the alternative pathway of complement with agrin and complement receptor 3 in the Alzheimer's disease brain

Abstract Factor H, a regulatory protein of the alternative pathway of complement (APC), is present in amyloid-β (Aβ) plaques in Alzheimer's disease (AD). Aβ plaques also contain significant amounts of heparan sulfate proteoglycans (HSPGs), such as agrin, as well as numerous activated microglia expressing increased levels complement receptor 3 (CR3). Here, we show the colocalization of each of these molecules in the AD brain and the functional capacity for these molecules to bind to one another in vitro. We propose that CR3 receptors expressed by microglia are used for ligand binding to factor H bound to HSPGs and Aβ in plaques in the AD brain.