Inflammatory mediators in the frontal lobe of patients with mixed and vascular dementia

Dement Geriatr Cogn Disord. 2008;25(3):278-86. doi: 10.1159/000118633. Epub 2008 Feb 26.

Abstract

Vascular dementia (VaD) accounts for about 20% of all dementias, and vascular risk is a key factor in more than 40% of people with Alzheimer's disease (AD). Little is known about inflammatory processes in the brains of these individuals. We have examined inflammatory mediators (interleukin (IL)-1beta, IL-1alpha, IL-6 and tumour necrosis factor alpha) and chemokines (macrophage inflammatory protein 1, monocyte chemo-attractant protein (MCP)-1 and granulocyte macrophage colony-stimulating factor) in brain homogenates from grey and white matter of the frontal cortex (Brodmann area 9) from patients with VaD (n = 11), those with concurrent VaD and AD (mixed dementia; n = 8) and from age-matched controls (n = 13) using ELISA assays. We found a dramatic reduction of MCP-1 levels in the grey matter in VaD and mixed dementia in comparison to controls (55 and 66%, respectively). IL-6 decreases were also observed in the grey matter of VaD and mixed dementia (72 and 71%, respectively), with a more modest decrease (30%) in the white matter of patients with VaD or mixed dementia. In the first study to examine the status of inflammatory mediators in a brain region severely affected by white-matter lesions, our findings highlight - in contrast to previous reports in AD - that patients at the later stage of VaD or mixed dementia have a significantly attenuated neuro-inflammatory response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chemokines / metabolism*
  • Dementia, Vascular / metabolism*
  • Dementia, Vascular / pathology*
  • Female
  • Frontal Lobe / metabolism*
  • Frontal Lobe / pathology*
  • Humans
  • Hydrogen-Ion Concentration
  • Interleukin-1 / metabolism*
  • Interleukin-1alpha / metabolism*
  • Interleukin-6 / metabolism*
  • Male
  • Microglia / metabolism
  • Microglia / pathology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Chemokines
  • Interleukin-1
  • Interleukin-1alpha
  • Interleukin-6
  • Tumor Necrosis Factor-alpha