title: The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer's disease.
abstract: Cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in Alzheimer's disease (AD). Vascular endothelial growth factor (VEGF), an angiogenic protein with important neurotrophic and neuroprotective actions, is under investigation as a therapeutic agent for the treatment of neurodegenerative disorders. The aim of this study was to generate encapsulated VEGF-secreting cells and implant them in a transgenic mouse model of AD, the double mutant amyloid precursor protein/presenilin 1 (APP/Ps1) mice, which shows a disturbed vessel homeostasis. We report that, after implantation of VEGF microcapsules, brain Abeta burden, hyperphosphorylated-tau and cognitive impairment attenuated in APP/Ps1 mice. Based on the neurovascular hypothesis, our findings suggest a new potential therapeutic approach that could be developed for AD, to enhance Abeta clearance and neurovascular repair, and to protect the cognitive behavior. Stereologically-implanted encapsulated VEGF-secreting cells could offer an alternative strategy in the treatment of AD.
authors.affiliation: Neuroscience Laboratory, Research Center, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Spuch
authors.forename: Desiree
authors.initials: D
authors.lastname: Antequera
authors.forename: Aitziber
authors.initials: A
authors.lastname: Portero
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
authors.forename: Rosa Ma
authors.initials: RM
authors.lastname: Hernández
authors.forename: Jose A
authors.initials: JA
authors.lastname: Molina
authors.forename: Felix
authors.initials: F
authors.lastname: Bermejo-Pareja
authors.forename: José L
authors.initials: JL
authors.lastname: Pedraz
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000464:Alginates / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000464:Alginates; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D042461:Vascular Endothelial Growth Factor A; C051546:alginate-polylysine-alginate; D011107:Polylysine