Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis

  • Paris D
  • Patel N
  • Delledonne A
 et al. 
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Abstract

Aβ peptides are naturally occurring peptides, which are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). In AD cases, levels of soluble and insoluble Aβ peptides increase in the brain as well as in the cerebrovasculature, a phenomenon that does not occur in extra-cranial vessels. There are frequently anomalies in the cerebrovasculature in AD, and despite increases in several pro-angiogenic factors in AD brain, evidence for increased vascularity is lacking; in fact there is evidence to the contrary. It has also been recently shown that Aβ peptides may have profound anti-angiogenic effects in vitro and in vivo. We therefore investigated whether there is evidence for altered angiogenesis in the vasculature in a transgenic mouse model of Aβ amyloidosis (Tg APPsw line 2576). In vitro, the formation of capillary-like structures on a reconstituted extracellular matrix by endothelial cells isolated from Tg APPsw is impaired. Ex vivo, the sprouting of new capillaries from arterial explants (over expressing Aβ) isolated from 9-month-old Tg APPsw is reduced compared to arterial explants isolated from control littermates. In addition, Tg APPsw mice show a reduction in vascular density in the cortex and hippocampus compared to control littermates. Altogether, our data suggest that the over expression of APPsw in the vasculature may oppose angiogenesis. © 2004 Elsevier Ireland Ltd. All rights reserved.

Author-supplied keywords

  • Alzheimer
  • Amyloid
  • Angiogenesis
  • Endothelial

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Authors

  • Daniel Paris

  • Nikunj Patel

  • Anthony Delledonne

  • Amita Quadros

  • Robert Smeed

  • Michael Mullan

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