Early intervention in the 3xTg-AD mice with an amyloid β-antibody fragment ameliorates first hallmarks of alzheimer disease

Lydia Giménez-Llort, Geovanny Rivera-Hernández, Marta Marin-Argany, José L. Sánchez-Quesada, Sandra Villegas

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)

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 short- and long-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. © 2013 Landes Bioscience.
Original languageEnglish
Pages (from-to)665-677
JournalmAbs
Volume5
DOIs
Publication statusPublished - 1 Sep 2013

Keywords

  • Alzheimer disease
  • Amyloid β oligomers
  • ApoE
  • ApoJ
  • Behavior
  • Clusterin
  • Immunotherapy
  • ScFv

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