title: VEGF significantly restores impaired memory behavior in Alzheimer's mice by improvement of vascular survival.
abstract: The functional impact of amyloid peptides (Aβs) on the vascular system is less understood despite these pathologic peptides are substantially deposited in the brain vasculature of Alzheimer's patients. Here we show substantial accumulation of Aβs 40 and 42 in the brain arterioles of Alzheimer's patients and of transgenic Alzheimer's mice. Purified Aβs 1-40 and 1-42 exhibited vascular regression activity in the in vivo animal models and vessel density was reversely correlated with numbers and sizes of amyloid plaques in human patients. A significant high number of vascular cells underwent cellular apoptosis in the brain vasculature of Alzheimer's patients. VEGF significantly prevented Aβ-induced endothelial apoptosis in vitro. Neuronal expression of VEGF in transgenic mice restored memory behavior of Alzheimer's. These findings provide conceptual implication of improvement of vascular functions as a novel therapeutic approach for the treatment of Alzheimer's disease.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Piotr
authors.initials: P
authors.lastname: Religa
authors.forename: Renhai
authors.initials: R
authors.lastname: Cao
authors.forename: Dorota
authors.initials: D
authors.lastname: Religa
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: David
authors.initials: D
authors.lastname: Westaway
authors.forename: Hugo H
authors.initials: HH
authors.lastname: Marti
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D016022:Case-Control Studies; D004195:Disease Models, Animal; D006801:Humans; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
chemical_list: D042461:Vascular Endothelial Growth Factor A