Neurosci Lett. 2004
Aug 5;366(1):80-5.
Impaired angiogenesis in a
transgenic mouse model of cerebral amyloidosis.
Paris D, Patel N, DelleDonne A, Quadros A, Smeed R, Mullan M.
The Roskamp Institute,
Abeta 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 Abeta 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 Abeta 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 Abeta 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 Abeta)
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.
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Keywords: Angiogenesis, transgenic mouse model, cerebral amyloidosis, Neuroscience Letters