Microglial cells internalize aggregates of the Alzheimer's disease amyloid beta-protein via a scavenger receptor.
Microglia are immune system cells associated with Alzheimer's disease plaques containing beta-amyloid (A beta). Murine microglia internalize microaggregates of fluorescently labeled or radioiodinated A beta peptide 1-42. Uptake was confirmed using aggregates of unlabeled A beta detected by immunofluorescence. Uptake of A beta was reduced by coincubation with excess acetyl-low density lipoprotein (Ac-LDL) or other scavenger receptor (SR) ligands, and Dil-labeled Ac-LDL uptake by microglia was blocked by excess A beta. CHO cells transfected with class A or B SRs showed significantly enhanced uptake of A beta. These results show that microglia express SRs that may play a significant role in the clearance of A beta plaques. Binding to SRs could activate inflammation responses that contribute to the pathology of Alzheimer's disease.
Paresce
D M
DM
Pathology Department, Columbia University, New York, New York 10032, USA.
Ghosh
R N
RN
Maxfield
F R
FR
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D002232:Carbocyanines; D008078:Cholesterol, LDL / Q000494:pharmacology; D005456:Fluorescent Dyes; D007425:Intracellular Membranes / Q000502:physiology; D007700:Kinetics; D008074:Lipoproteins / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000737:chemistry* / Q000502:physiology*; D009154:Mutation; D011134:Polysaccharides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000970:Antineoplastic Agents; D002232:Carbocyanines; D008078:Cholesterol, LDL; D005456:Fluorescent Dyes; D008074:Lipoproteins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D000511:alpha-Macroglobulins; C097511:didodecylindocarbocyanine; C007789:fucoidan