PT  - JOURNAL ARTICLE
AU  - Daniel Paris
AU  - Nowel Ganey
AU  - Magdalena Banasiak
AU  - Vincent Laporte
AU  - Nikunj Patel
AU  - Myles Mullan
AU  - Susan F. Murphy
AU  - Gi-Taek Yee
AU  - Corbin Bachmeier
AU  - Christopher Ganey
AU  - David Beaulieu-Abdelahad
AU  - Venkatarajan S. Mathura
AU  - Steven Brem
AU  - Michael Mullan
TI  - Impaired Orthotopic Glioma Growth and Vascularization in Transgenic Mouse Models of Alzheimer's Disease
AID  - 10.1523/JNEUROSCI.2586-10.2010
DP  - 2010 Aug 25
TA  - The Journal of Neuroscience
PG  - 11251--11258
VI  - 30
IP  - 34
4099  - http://www.jneurosci.org/content/30/34/11251.short
4100  - http://www.jneurosci.org/content/30/34/11251.full
SO  - J. Neurosci.2010 Aug 25; 30
AB  - 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 β-amyloid (Aβ) 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 Aβ 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 Aβ 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 Aβ 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.