Increased Fibrillar b-Amyloid in Response to Human C1q Injections into Hippocampus and Cortex of APP1PS1 Transgenic Mice*

Human C1q when injected directly into hippocampus and cortex of doubly transgenic APP1PS1 mice results in the increase of Congo red–positive fibrillar deposits. Although there was no significant change in overall area stained for Ab total, qualitatively it appeared that there was less diffuse Ab in C1q-treated mice versus vehicle. There was no apparent change in astroglial or microglial activation caused by injection of C1q with respect to vehicle injections. These effects of C1q were only found in 50% BUB/BnJ mice, a strain with higher serum complement activity than other mouse lines. These in vivo data were consistent with the effects of C1q to increase fibrillogenesis of Ab in vitro. In conclusion, complement protein C1q, believed to be involved in the pathogenesis of Alzheimer’s disease in humans, can cause increased fibrillogenesis in the APP1PS1 mouse model of amyloid deposition.