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Journal of Clinical Immunology

, Volume 19, Issue 4, pp 223–230 | Cite as

Intracerebral Production of Tumor Necrosis Factor-α, a Local Neuroprotective Agent, in Alzheimer Disease and Vascular Dementia

  • Elisabeth Tarkowski
  • Kaj Blennow
  • Anders Wallin
  • Andrzej Tarkowski
Article

Abstract

The local pattern of proinflammatory cytokine release was studied in Alzheimer disease (AD) and vascular dementia (VAD), by measuring intrathecal levels of IL-1β, IL-6, TNF-α, and its naturally occurring antagonists, soluble TNF receptors I and II. The cytokine levels were related to neuronal damage, as measured by the intrathecal tau concentration, to cerebral apoptosis assessed by levels of Fas/APO-1 and bcl-2, and to clinical variables. In vitro analysis was performed to study the effect of TNF-α on the production of bcl-2, an antiapoptotic factor, by human neuronal cells. Patients with both AD and VAD displayed significantly higher intrathecal levels of TNF-α compared to controls. In addition, patients with AD showed significantly negative correlations between the intrathecal levels of TNF-α and the levels of Fas/APO-1 as well as of tau protein. The level of bcl-2 in supernatants of TNF-α-exposed cultures of human neuronal cells was up to three times higher than in control supernatants. Our study demonstrates intrathecal production of TNF-α in patients with dementias, suggesting that this cytokine may have a neuroprotective role in these neurodegenerative conditions as evidenced by negative correlations between this cytokine and (i) levels of intrathecal Fas/APO-1 and (ii) levels of tau protein, both parameters closely related to brain damage. Our in vitro data suggest that TNF-α exerts its neuroprotective effect by stimulating neuronal cells to express bcl-2, a molecule which downregulates apoptosis.

Dementia tumor necrosis factor-α apoptosis tau protein 

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Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Elisabeth Tarkowski
    • 1
  • Kaj Blennow
    • 2
  • Anders Wallin
    • 2
  • Andrzej Tarkowski
    • 1
  1. 1.Department of RheumatologyUniversity of Göteborg and Hospital of VarbergSweden
  2. 2.Department of Clinical Neurosciences (Section of Psychiatry and Neurochemistry)University of GöteborgSweden

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