Complement component C1q modulates the phagocytosis of Aβ by microglia

Recent studies showing that microglia internalize the amyloid beta-peptide (A beta) suggest that these cells have the potential for clearing Ap deposits in Alzheimer's disease, and mechanisms that regulate the removal of A beta may therefore be of clinical interest. Previous studies from this laboratory showing that C1q enhances phagocytosis of cellular targets by rat microglia prompted the current investigations characterizing the effects of C1q on microglial phagocytosis of A beta. Microglia were shown to phagocytose A beta 1-42, in agreement with observations of other investigators. Uptake of A beta 1-42 was observed for concentrations of 5-50 mu M, and phagocytosis of peptides containing C-14 or fluorescein (FM) labels was not affected by the interaction of microglia with C1q-coated surfaces. However, inclusion of C1q (125 nM-1.4 mu M) in solutions of 50 mu M A beta 1-42 inhibited the uptake of C-14-A beta 1-42 and FM-A beta 1-42, suggesting that C1q blocks the interaction of A beta with microglia. Uptake of A beta was partially blocked by the scavenger receptor ligands polyinosinic acid and maleylated BSA. Inhibition of A beta uptake by C1q may contribute to the accumulation of fibrillar, C1q-containing plaques that occurs in parallel with disease progression. These data suggest that mechanisms which interfere with the binding of C1q to A beta may be of therapeutic value both through inhibition of the inflammatory events resulting from complement activation and via altered access of A beta sites necessary for ingestion by microglia. (C) 2000 Academie Press.