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Early intervention in the 3xTg-AD mice with an amyloid β-antibody fragment ameliorates first hallmarks of Alzheimer disease
Giménez Llort, Lydia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Rivera Hernández, Geovanny (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Marin Argany, Marta (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Sánchez Quesada, José Luis (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya). Departament de Bioquímica)
Villegas Hernández, Sandra (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data: 2013
Resum: 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.
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.
Nota: Número d'acord de subvenció ISCIII/FEDER/PI10/00975
Nota: Número d'acord de subvenció ISCIII/FEDER/PI10/00265
Nota: Número d'acord de subvenció ISCIII/FEDER/PI10/00283
Nota: Número d'acord de subvenció AGAUR/2009-SGR-00761
Nota: Número d'acord de subvenció AGAUR/2009-SGR-42271
Drets: Tots els drets reservats.
Llengua: Anglès
Document: article ; recerca ; submittedVersion
Matèria: Alzheimer disease ; Amyloid β oligomers ; ApoE ; ApoJ ; Behavior ; Clusterin ; Immunotherapy ; ScFv
Publicat a: mAbs, Vol. 5 Issue 5(Sep 2013) , p. 665-864, ISSN 1942-0862

DOI: 10.4161/mabs.25424

44 p, 2.3 MB

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