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(American Journal of Pathology. 2002;160:1583-1587.)
© 2002 American Society for Investigative Pathology

Short Communication

Cerebrovascular Transforming Growth Factor-ß Contributes to Inflammation in the Alzheimer’s Disease Brain

Paula Grammas^* and Roma Ovase^*

From the Department of Pathology^*and the Oklahoma Center for Neuroscience,University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

Inflammatory mechanisms are thought to contribute to lesion pathogenesis and neuronal cell death in Alzheimer’s disease. Transforming growth factor-ß (TGF-ß) plays a central role in the response of the brain to injury, and is increased in the brain in Alzheimer’s disease. In this study we determine whether expression of TGF-ß is abnormal in the microvasculature in Alzheimer’s disease and whether TGF-ß affects vascular production of pro-inflammatory cytokines, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-. Microvessels isolated from the cortices of Alzheimer’s disease patients and age-matched controls are analyzed for microvessel-associated and released TGF-ß. Results from Western blot analysis and enzyme-linked immunosorbent assay indicate a higher level of TGF-ß in Alzheimer’s disease vessels compared to controls. To determine whether TGF-ß affects vascular release of inflammatory factors, cultured brain endothelial cells are treated with TGF-ß and levels of IL-1ß and TNF- determined. Both enzyme-linked immunosorbent assay and Western blot analyses show that untreated endothelial cells express little IL-1ß or TNF-, but incubation with TGF-ß results in robust expression of these factors by brain endothelial cells. Our results suggest that vessel-derived TGF-ß contributes to inflammatory processes in the Alzheimer brain.

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