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 beta-amyloid (fAbeta) and other components such as complement proteins. We have shown previously that murine microglia bind and internalize fAbeta microaggregates via the type A scavenger receptor, but degradation of internalized fAbeta is significantly slower than normal degradation. In this study, we compared internalization by microglia of fAbeta microaggregates to that of anti-Abeta-antibody-coated fAbeta (IgG-fAbeta) microaggregates and found that the uptake of the latter is increased by about 1.5-fold versus unmodified fAbeta. The endocytic trafficking of IgG-fAbeta is similar to that of fAbeta microaggregates, following an endosomal/lysosomal pathway. We also compared the internalization of fAbeta microaggregates to that of complement protein, C1q-coated fAbeta microaggregates, and found that the levels of uptake are also increased by about 1.5-fold. Rates of degradation of both types of modified fAbeta microaggregates are unchanged compared with unmodified fAbeta microaggregates. We demonstrated by blocking studies that internalization of IgG-fAbeta is mediated by Fc receptors. These data suggest that, in vivo, several different microglial receptors may play a part in internalizing fAbeta, but the involvement of other receptors may not increase the degradation of fAbeta.
Brazil
M I
MI
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.
Chung
H
H
Maxfield
F R
FR
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015922:Complement C1q / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism
D000682:Amyloid; D007074:Immunoglobulin G; D011961:Receptors, Fc; D015922:Complement C1q