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Página principal > Artículos > Artículos publicados > Early intervention in the 3xTg-AD mice with an amyloid β-antibody fragment ameliorates first hallmarks of Alzheimer disease |
Fecha: | 2013 |
Resumen: | The single-chain variable fragment, scFv-h3D6, has been shown to prevent in vitro toxicity induced by the amyloid β (Aβ) peptide in neuroblastoma cell cultures by withdrawing Aβ oligomers from the amyloid pathway. Present study examined the in vivo effects of scFv-h3D6 in the triple-transgenic 3xTg-AD mouse model of Alzheimer disease. Prior to the treatment, five-month-old female animals, corresponding to early stages of the disease, showed the first behavioral and psychological symptoms of dementia -like behaviors. Cognitive deficits included long- and short-term learning and memory deficits and high swimming navigation speed. After a single intraperitoneal dose of scFv-h3D6, the swimming speed was reversed to normal levels and the learning and memory deficits were ameliorated. Brain tissues of these animals revealed a global decrease of Aβ oligomers in the cortex and olfactory bulb after treatment, but this was not seen in the hippocampus and cerebellum. In the untreated 3xTg-AD animals, we observed an increase of both apoJ and apoE concentrations in the cortex, as well as an increase of apoE in the hippocampus. Treatment significantly recovered the non-pathological levels of these apolipoproteins. Our results suggest that the benefit of scFv-h3D6 occurs at both behavioral and molecular levels. |
Ayudas: | Instituto de Salud Carlos III FEDER/PI10/00975 Instituto de Salud Carlos III FEDER/PI10/00265 Instituto de Salud Carlos III FEDER/PI10/00283 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-00761 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-42271 |
Nota: | This work was supported by FMM-2008; FEDER (FISPI10-00975, -00265 and -00283); SGR2009-00761 and -42271. G.R-H is supported by a MAEC-AECI fellowship (Spanish government) and M.M-A by a PIF (UAB, Spain) fellowship. |
Derechos: | Tots els drets reservats. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió sotmesa a revisió |
Materia: | Alzheimer disease ; Amyloid β oligomers ; ApoE ; ApoJ ; Behavior ; Clusterin ; Immunotherapy ; ScFv |
Publicado en: | MAbs, Vol. 5 Issue 5(Sep 2013) , p. 665-864, ISSN 1942-0870 |
Pre-print 44 p, 2.3 MB |