title: Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis.
abstract: 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.
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. dparis@rdfn.org
authors.forename: Daniel
authors.initials: D
authors.lastname: Paris
authors.forename: Nikunj
authors.initials: N
authors.lastname: Patel
authors.forename: Anthony
authors.initials: A
authors.lastname: DelleDonne
authors.forename: Amita
authors.initials: A
authors.lastname: Quadros
authors.forename: Robert
authors.initials: R
authors.lastname: Smeed
authors.forename: Michael
authors.initials: M
authors.lastname: Mullan
mesh_terms: D000375:Aging / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000473:pathology; D006624:Hippocampus / Q000098:blood supply; D066298:In Vitro Techniques; D007797:Laminin; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans; D014684:Venae Cavae / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen