title: Early intervention in the 3xTg-AD mice with an amyloid β-antibody fragment ameliorates first hallmarks of Alzheimer disease.
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.
authors.affiliation: Institut de Neurociències; Unitat de Biociències; Universitat Autònoma de Barcelona; Barcelona, Spain; Departament de Psiquiatria i Medicina Legal; Unitat de Biociències; Universitat Autònoma de Barcelona; Barcelona, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Giménez-Llort
authors.forename: Geovanny
authors.initials: G
authors.lastname: Rivera-Hernández
authors.forename: Marta
authors.initials: M
authors.lastname: Marin-Argany
authors.forename: José L
authors.initials: JL
authors.lastname: Sánchez-Quesada
authors.forename: Sandra
authors.initials: S
authors.lastname: Villegas
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051152:Clusterin / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000276:immunology / Q000494:pharmacology*; D013550:Swimming; D013997:Time Factors; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D051152:Clusterin; D053764:Presenilin-1; D057127:Single-Chain Antibodies; D016875:tau Proteins
keywords: Alzheimer disease; amyloid β oligomers; apoE; apoJ; behavior; clusterin; immunotherapy; scFv