Alzheimer's disease (AD) is the most common form of dementia among the aging 
population and is characterized pathologically by the progressive intracerebral 
accumulation of beta-amyloid (Abeta) peptides and neurofibrillary tangles. The 
level of proangiogenic growth factors and inflammatory mediators with 
proangiogenic activity is known to be elevated in AD brains which has led to the 
supposition that the cerebrovasculature of AD patients is in a proangiogenic 
state. However, angiogenesis depends on the balance between proangiogenic and 
antiangiogenic factors and the brains of AD patients also show an accumulation 
of endostatin and Abeta peptides which have been shown to be antiangiogenic. To 
determine whether angiogenesis is compromised in the brains of two transgenic 
mouse models of AD overproducing Abeta peptides (Tg APPsw and Tg PS1/APPsw 
mice), we assessed the growth and vascularization of orthotopically implanted 
murine gliomas since they require a high degree of angiogenesis to sustain their 
growth. Our data reveal that intracranial tumor growth and angiogenesis is 
significantly reduced in Tg APPsw and Tg PS1/APPsw mice compared with their 
wild-type littermates. In addition, we show that Abeta inhibits the angiogenesis 
stimulated by glioma cells when cocultured with human brain microvascular cells 
on a Matrigel layer. Altogether our data suggest that the brain of transgenic 
mouse models of AD does not constitute a favorable environment to support 
neoangiogenesis and may explain why vascular insults synergistically precipitate 
the cognitive presentation of AD.