Effects of Incorporation of Immunoglobulin G and Complement Component C1q on Uptake and Degradation of Alzheimer's Disease Amyloid Fibrils by Microglia*

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

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