Amyloid-beta induces chemokine secretion and monocyte migration across a human blood--brain barrier model

Mol Med. 1998 Jul;4(7):480-9.


Background: Aside from numerous parenchymal and vascular deposits of amyloid beta (A beta) peptide, neurofibrillary tangles, and neuronal and synaptic loss, the neuropathology of Alzheimer's disease is accompanied by a subtle and chronic inflammatory reaction that manifests itself as microglial activation. However, in Alzheimer's disease, alterations in the permeability of the blood-brain barrier and chemotaxis, in part mediated by chemokines and cytokines, may permit the recruitment and transendothelial passage of peripheral cells into the brain parenchyma.

Materials and methods: Human monocytes from different donors were tested for their capacity to differentiate into macrophages and their ability to secrete cytokines and chemokines in the presence of A beta 1-42. A paradigm of the blood-brain barrier was constructed utilizing human brain endothelial and astroglial cells with the anatomical and physiological characteristics observed in vivo. This model was used to test the ability of monocytes/macrophages to transmigrate when challenged by A beta 1-42 on the brain side of the blood-brain barrier model.

Results: In cultures of peripheral monocytes, A beta 1-42 induced the secretion of proinflammatory cytokines TNF-alpha, IL-6, IL-1 beta, and IL-12, as well as CC chemokines MCP-1, MIP-1 alpha, and MIP-1 beta, and CXC chemokine IL-8 in a dose-related fashion. In the blood-brain barrier model, A beta 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. A beta 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of A beta 1-42 varied dramatically with monocytes from different donors.

Conclusion: In some individuals, circulating monocytes/macrophages, when recruited by chemokines produced by activated microglia and macrophages, could add to the inflammatory destruction of the brain in Alzheimer's disease.

MeSH terms

  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / pharmacology*
  • Astrocytes / physiology
  • Blood-Brain Barrier*
  • Cell Differentiation
  • Cell Movement*
  • Cells, Cultured
  • Chemokines / metabolism*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / physiology
  • Humans
  • Inflammation
  • Interleukins / metabolism
  • Macrophages / cytology
  • Macrophages / physiology
  • Models, Biological
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Monocytes / physiology
  • Peptide Fragments / pharmacology*
  • Permeability
  • Tumor Necrosis Factor-alpha / metabolism


  • Amyloid beta-Peptides
  • Chemokines
  • Interleukins
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • amyloid beta-protein (1-42)