Web of Science: 30 citations, Scopus: 32 citations, Google Scholar: citations,
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 Biologia Molecular)

Date: 2013
Abstract: 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.
Note: 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.
Note: Número d'acord de subvenció ISCIII/FEDER/PI10/00975
Note: Número d'acord de subvenció ISCIII/FEDER/PI10/00265
Note: Número d'acord de subvenció ISCIII/FEDER/PI10/00283
Note: Número d'acord de subvenció AGAUR/2009/SGR-00761
Note: Número d'acord de subvenció AGAUR/2009/SGR-42271
Rights: Tots els drets reservats.
Language: Anglès.
Document: article ; recerca ; submittedVersion
Subject: Alzheimer disease ; Amyloid β oligomers ; ApoE ; ApoJ ; Behavior ; Clusterin ; Immunotherapy ; ScFv
Published in: mAbs, Vol. 5 Issue 5(Sep 2013) , p. 665-864, ISSN 1942-0862

DOI: 10.4161/mabs.25424
PMID: 23884018


Pre-print
44 p, 2.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2016-02-01, last modified 2019-02-03



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