Microglia are macrophage-like immune system cells found in the brain. They are associated with Alzheimer's Disease plaques, which contain fibrillar -amyloid (fA) and other components such as complement proteins. We have shown previously that murine microglia bind and internalize fA microaggregates via the type A scavenger receptor, but degradation of internalized fA is significantly slower than normal degradation. In this study, we compared internalization by microglia of fA microaggregates to that of anti-A-antibody-coated fA (IgG-fA) microaggregates and found that the uptake of the latter is increased by about 1.5-fold versus unmodified fA. The endocytic trafficking of IgG-fA is similar to that of fA microaggregates, following an endosomal/lysosomal pathway. We also compared the internalization of fA microaggregates to that of complement protein, C1q-coated fA microaggregates, and found that the levels of uptake are also increased by about 1.5-fold. Rates of degradation of both types of modified fA microaggregates are unchanged compared with unmodified fA microaggregates. We demonstrated by blocking studies that internalization of IgG-fA is mediated by Fc receptors. These data suggest that, in vivo, several different microglial receptors may play a part in internalizing fA, but the involvement of other receptors may not increase the degradation of fA.
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