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

Milan Fiala, Ling Zhang, Xiaohu Gan, Barbara Sherry, Dennis Taub, Michael C. Graves, Suzan Hama, Dennis Way, Martin Weinand, Marlys Witte, Diane Lorton, Yu Min Kuo, Alex E. Roher

Research output: Contribution to journalArticlepeer-review

206 Citations (Scopus)


Background: Aside from numerous parenchymal and vascular deposits of amyloid β (Aβ) 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 Aβ 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 Aβ 1-42 on the brain side of the blood-brain barrier model. Results: In cultures of peripheral monocytes, Aβ 1-42 induced the secretion of proinflammatory cytokines TNF-a, IL-6, IL-1β, and IL-12, as well as CC chemokines MCP-1, MIP-1α, and MIP-1β, and CXC chemokine IL-8 in a dose- related fashion. In the blood-brain barrier model, Aβ 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. Aβ 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of Aβ 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.

Original languageEnglish
Pages (from-to)480-489
Number of pages10
JournalMolecular Medicine
Issue number7
Publication statusPublished - 1998

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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