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

D. W. Dickson, S. C. Lee, L. A. Mattiace, S. H. Yen, C. Brosnan

Research output: Contribution to journalArticle

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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-beta and tumor necrosis factor-alpha). 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 of 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
StatePublished - Jan 1993

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Microglia
Alzheimer Disease
Acquired Immunodeficiency Syndrome
Cytokines
HIV-1
Central Nervous System
Pathology
HIV Receptors
Infection
Viral Antibodies
Gliosis
Viral Antigens
Immunoglobulin Isotypes
Spinal Cord Diseases
Poisons
Histocompatibility Antigens Class II
Amyloid Plaques
Viral Proteins
Virus Diseases
Giant Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Dickson, D. W., Lee, S. C., Mattiace, L. A., Yen, S. H., & Brosnan, C. (1993). Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. GLIA, 7(1), 75-83.

Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. / Dickson, D. W.; Lee, S. C.; Mattiace, L. A.; Yen, S. H.; Brosnan, C.

In: GLIA, Vol. 7, No. 1, 01.1993, p. 75-83.

Research output: Contribution to journalArticle

Dickson, DW, Lee, SC, Mattiace, LA, Yen, SH & Brosnan, C 1993, 'Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease.', GLIA, vol. 7, no. 1, pp. 75-83.
Dickson DW, Lee SC, Mattiace LA, Yen SH, Brosnan C. Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. GLIA. 1993 Jan;7(1):75-83.
Dickson, D. W. ; Lee, S. C. ; Mattiace, L. A. ; Yen, S. H. ; Brosnan, C. / Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. In: GLIA. 1993 ; Vol. 7, No. 1. pp. 75-83.
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