Microglial cells internalize aggregates of the Alzheimer's disease amyloid beta-protein via a scavenger receptor

Neuron. 1996 Sep;17(3):553-65. doi: 10.1016/s0896-6273(00)80187-7.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Biological Transport / physiology
  • Brain Chemistry / physiology
  • Carbocyanines
  • Cholesterol, LDL / pharmacology
  • Fluorescent Dyes
  • Intracellular Membranes / physiology
  • Kinetics
  • Lipoproteins / pharmacology
  • Mice
  • Microglia / chemistry*
  • Microglia / physiology*
  • Mutation
  • Polysaccharides / pharmacology
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / physiology*
  • alpha-Macroglobulins / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Antineoplastic Agents
  • Carbocyanines
  • Cholesterol, LDL
  • Fluorescent Dyes
  • Lipoproteins
  • Polysaccharides
  • Receptors, Cell Surface
  • alpha-Macroglobulins
  • didodecylindocarbocyanine
  • fucoidan