Reduced brain tissue perfusion in TGF-beta 1 transgenic mice showing Alzheimer's disease-like cerebrovascular abnormalities

Neurobiol Dis. 2005 Jun-Jul;19(1-2):38-46. doi: 10.1016/j.nbd.2004.11.008.

Abstract

We have studied the functional repercussions of cerebrovascular abnormalities in transgenic mice overexpressing TGF-beta1. These mice develop Alzheimer's disease-like vascular and meningeal alterations without parenchymal degeneration. Autoradiographic cerebral blood flow measurements in 9-month-old TGF-beta1 mice compared to non-transgenic littermates provided evidence of reduced tissue perfusion, most prominent in limbic regions. A highly significant inverse correlation was found between the density of thioflavin-S-positive blood vessels and blood flow in the hippocampus and the cortex. An inverse correlation was likewise found between meningeal staining and blood flow in thalamic nuclei and regions of high blood flow. Thus, the vascular abnormalities were associated locally with reduced perfusion rate and more widely with limitation in the blood flow. These chronic changes may be related to fibrillar and soluble A beta peptides, the amount of which was almost doubled in the brains of TGF-beta1 mice. Comparison with previous results of cerebral glucose utilization in TGF-beta1 mice shows that reduced utilization preferentially occurred in regions with a high metabolic rate and a relatively low blood flow, suggesting that the metabolic needs are not met by blood supply in these regions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Animals
  • Brain / blood supply*
  • Brain / metabolism*
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / metabolism
  • Mice
  • Mice, Transgenic
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta1

Substances

  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1