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.