title: Inflammatory mediators in the frontal lobe of patients with mixed and vascular dementia.
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.
authors.affiliation: Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Ezra
authors.initials: E
authors.lastname: Mulugeta
authors.forename: Francisco
authors.initials: F
authors.lastname: Molina-Holgado
authors.forename: Mark S
authors.initials: MS
authors.lastname: Elliott
authors.forename: Tibor
authors.initials: T
authors.lastname: Hortobagyi
authors.forename: Robert
authors.initials: R
authors.lastname: Perry
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: Clive G
authors.initials: CG
authors.lastname: Ballard
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
mesh_terms: D000368:Aged; D018925:Chemokines / Q000378:metabolism*; D015140:Dementia, Vascular / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018925:Chemokines; D007375:Interleukin-1; D053582:Interleukin-1alpha; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha