Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease

Dennis W. Dickson, Sunhee C. Lee, Linda A. Mattiace, Shu‐Hui C. Yen, Celia Brosnan

Research output: Contribution to journalArticle

761 Scopus citations

Abstract

Microglia are associated with central nervous system (CNS) pathology of both Alzheimer's disease (AD) and the acquired immunodeficiency syndrome (AIDS). In AD, microglia, especially those associated with amyloid deposits, have a phenotype that is consistent with a state of activation, including immunoreactivity with antibodies to class II major histocompatibility antigens and to inflammatory cytokines (interleukin‐1‐β and tumor necrosis factor‐α). Evidence from other studies in rodents indicate that microglia can be activated by neuronal degeneration. These results suggest that microglial activation in AD may be secondary to neurodegeneration and that, once activated, microglia may participate in a local inflammatory cascade that promotes tissue damage and contributes to amyloid formation. In AIDS, microglia are the primary target of retroviral infection. Both ramified and ameboid microglia, in addition to multinucleated giant cells, are infected by the human immunodeficiency virus (HIV‐1). The mechanism of microglial infection is not known since microglia lack CD4, the HIV‐1 receptor. Microglia display high affinity receptors for immunoglobulins, which makes antibody‐mediated viral uptake a possible mechanism of infection. In AIDS, the extent of active viral infection and cytokine production may be critically dependent upon other factors, such as the presence of coinfecting agents. In the latter circumstance, very severe CNS pathology may emerge, including necrotizing lesions. In other circumstances, HIV infection microglia probably leads to CNS pathology by indirect mechanisms, including release of viral proteins (gp120) and toxic cytokines. Such a mechanism is the best hypothesis for the pathogenesis of vacuolar myelopathy in adults and the diffuse gliosis that characterizes pediatric AIDS, in which very little viral antigen can be detected.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalGlia
Volume7
Issue number1
DOIs
StatePublished - Jan 1993

Keywords

  • Amyloid deposits
  • CNS pathology
  • Coinfecting agents
  • HLA‐DR
  • Neuronal degeneration

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Dickson, D. W., Lee, S. C., Mattiace, L. A., Yen, SH. C., & Brosnan, C. (1993). Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia, 7(1), 75-83. https://doi.org/10.1002/glia.440070113