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 microglia appear to be involved in the later stages of plaque development. Since tissue macrophages are known to synthesize C1q, cultured rat microglia were examined for C1q immunoreactivity. Anti-C1q staining was detected, particularly in process-bearing microglia, indicating constitutive expression of C1q. Thus, microglia could provide a source of C1q for plaques even before becoming reactive. Since it has been previously 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 formation of amyloid deposits on these cells. While electron microscopic analysis of negatively stained amyloid fibrils confirmed that pre-incubation 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 that is known to modulate phagocytosis was found and was up-regulated in non-process-bearing microglia by interferon-gamma. While these data exclude a role for the C1q receptor in beta 1-42 toxicity in microglia, the observed expression and up-regulation of C1q receptor on microglia by interferon-gamma would be consistent with a role for C1q in complement-mediated inflammatory responses in AD and as a potential activator of microglial function in plaques.
Korotzer
A R
AR
IRU in Brain Aging, University of California at Irvine 92717, USA.
Watt
J
J
Cribbs
D
D
Tenner
A J
AJ
Burdick
D
D
Glabe
C
C
Cotman
C W
CW
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D015922:Complement C1q / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007372:Interferons / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008854:Microscopy, Electron; D016874:Neurofibrillary Tangles / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011951:Receptors, Complement / Q000096:biosynthesis*
D016229:Amyloid beta-Peptides; D011951:Receptors, Complement; D015922:Complement C1q; D007372:Interferons