Inflammatory factors are elevated in brain microvessels in Alzheimer's disease.
In Alzheimer's disease (AD) inflammatory processes occur in pathologically vulnerable brain regions. The objective of this study is to compare both the release and the presence of microvessel-associated cytokines in vessels isolated from the brains of AD patients to microvessels from control brains. Microvessels are isolated from the cortices of AD patients and age-matched controls, without evidence of neurodegenerative disease. Inflammatory factors in the media are quantitated by ELISA and microvessel-associated mediators assessed by Western blot. Our results demonstrate that unstimulated AD microvessels release significantly higher levels of interleukin-1beta-(IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) compared to non-AD microvessels. Levels of microvessel-associated monocyte chemoattractant protein (MCP-1) and IL-1beta are high in AD-derived microvessels, but not detectable in non-AD microvessels. These results suggest that the cerebral microcirculation contributes inflammatory mediators to the milieu of the AD brain and may be involved in the pathogenesis of neuronal injury and death in this disorder.
Grammas
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Department of Pathology, University of Oklahoma Health Sciences Center, 975 N.E. 10th Street, Oklahoma City, OK 73104, USA. paula-grammas@ouhsc.edu
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D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002196:Capillaries / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha