Association of factor H of the alternative pathway of complement with agrin and complement receptor 3 in the Alzheimer's disease brain.
Factor H, a regulatory protein of the alternative pathway of complement (APC), is present in amyloid-beta (Abeta) plaques in Alzheimer's disease (AD). Abeta 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 Abeta in plaques in the AD brain.
Strohmeyer
Ron
R
L.J. Roberts Alzheimer's Center, Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA.
Ramirez
Mauricio
M
Cole
Gregory J
GJ
Mueller
Kyle
K
Rogers
Joseph
J
D000368:Aged; D018171:Agrin / Q000032:analysis* / Q000378:metabolism; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D001923:Brain Chemistry; D017242:Complement Factor H / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D003170:Complement Pathway, Alternative; D006801:Humans; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000032:analysis*; D009457:Neuroglia / Q000276:immunology
D018171:Agrin; D016229:Amyloid beta-Peptides; C493495:CFH protein, human; D016177:Macrophage-1 Antigen; D017242:Complement Factor H