Cerebrovascular transforming growth factor-beta contributes to inflammation in the Alzheimer's disease brain

Am J Pathol. 2002 May;160(5):1583-7. doi: 10.1016/s0002-9440(10)61105-4.


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

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Blood Vessels / chemistry*
  • Blood Vessels / pathology
  • Blotting, Western
  • Brain / blood supply*
  • Brain / pathology
  • Cells, Cultured
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • In Vitro Techniques
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Interleukin-1 / metabolism
  • Transforming Growth Factor beta / analysis*
  • Transforming Growth Factor beta / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Interleukin-1
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha