CULTURED RAT MICROGLIA EXPRESS C1Q AND RECEPTOR FOR C1Q - IMPLICATIONS FOR AMYLOID EFFECTS ON MICROGLIA

Senile plaques, the pathological hallmark of Alzheimer's disease (AD), are associated with complement components, including C1q. Reactive mi croglia appear to be involved in the later stages of plaque developmen t. Since tissue macrophages are known to synthesize C1q, cultured rat microglia were examined for C1q immunoreactivity. Anti-C1q staining wa s detected, particularly in process-bearing microglia, indicating cons titutive expression of C1q. Thus, microglia could provide a source of C1q for plaques even before becoming reactive. Since it has been previ ously shown that C1q binds beta 1-42, the major constituent of senile plaques, and since beta 1-42 is toxic to microglia in vitro, we asked if preincubation of beta 1-42 with C1q alters either metabolic indices of amyloid-induced degeneration in microglial cultures or the formati on of amyloid deposits on these cells. While electron microscopic anal ysis of negatively stained amyloid fibrils confirmed that preincubatio n with C1q induced the association of C1q with the fibrils, no effect of the binding of C1q to beta 1-42 on beta 1-42 toxicity in microglia was observed. Interestingly, immunoreactivity for the C1q receptor tha t is known to modulate phagocytosis was found and was up-regulated in non-process-bearing microglia by interferon-gamma. While these data ex clude a role for the C1q receptor in beta 1-42 toxicity in microglia, the observed expression and up-regulation of C1q receptor oh microglia by interferon-gamma would be consistent with a role for C1q in comple ment-mediated inflammatory responses in AD and as a potential activato r of microglial function in plaques. (C) 1995 Academic Press, Inc.