Complement component C1q modulates the phagocytosis of A beta by microglia

Recent studies showing that microglia internalize the amyloid beta-peptide (A beta) suggest that these cells have the potential for clearing Ap deposi ts in Alzheimer's disease, and mechanisms that regulate the removal of A be ta may therefore be of clinical interest. Previous studies from this labora tory showing that C1q enhances phagocytosis of cellular targets by rat micr oglia 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 phagocytos is of peptides containing C-14 or fluorescein (FM) labels was not affected by the interaction of microglia with C1q-coated surfaces. However, inclusio n of C1q (125 nM-1.4 mu M) in solutions of 50 mu M A beta 1-42 inhibited th e 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 b locked by the scavenger receptor ligands polyinosinic acid and maleylated B SA. Inhibition of A beta uptake by C1q may contribute to the accumulation o f fibrillar, C1q-containing plaques that occurs in parallel with disease pr ogression. These data suggest that mechanisms which interfere with the bind ing of C1q to A beta may be of therapeutic value both through inhibition of the inflammatory events resulting from complement activation and via alter ed access of A beta sites necessary for ingestion by microglia. (C) 2000 Ac ademie Press.