TY - JOUR
T1 - Early intervention in the 3xTg-AD mice with an amyloid β-antibody fragment ameliorates first hallmarks of alzheimer disease
AU - Giménez-Llort, Lydia
AU - Rivera-Hernández, Geovanny
AU - Marin-Argany, Marta
AU - Sánchez-Quesada, José L.
AU - Villegas, Sandra
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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.
AB - 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.
KW - Alzheimer disease
KW - Amyloid β oligomers
KW - ApoE
KW - ApoJ
KW - Behavior
KW - Clusterin
KW - Immunotherapy
KW - ScFv
U2 - https://doi.org/10.4161/mabs.25424
DO - https://doi.org/10.4161/mabs.25424
M3 - Article
VL - 5
SP - 665
EP - 677
JO - mAbs
JF - mAbs
SN - 1942-0862
ER -