The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer's disease.
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.
Spuch
Carlos
C
Neuroscience Laboratory, Research Center, Hospital 12 de Octubre, Madrid, Spain.
Antequera
Desiree
D
Portero
Aitziber
A
Orive
Gorka
G
Hernández
Rosa Ma
RM
Molina
Jose A
JA
Bermejo-Pareja
Felix
F
Pedraz
José L
JL
Carro
Eva
E
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*
D000464:Alginates; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D042461:Vascular Endothelial Growth Factor A; C051546:alginate-polylysine-alginate; D011107:Polylysine