Treatment with scFv-h3D6 Prevented Neuronal Loss and Improved Spatial Memory in Young 3xTg-AD Mice by Reducing the Intracellular Amyloid-β Burden
Esquerda-Canals, Gisela (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Roda, Alejandro Ramos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Martí-Clúa, Joaquín (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Montoliu-Gaya, Laia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Rivera-Hernández, Geovanny (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Villegas Hernández, Sandra (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2019
Description:	23 pàg.
Abstract:	The intracellular deposition of amyloid-beta (A beta) peptides has been described in the brains of both Alzheimer's disease (AD) patients and animal models. A correlation between the intracellular amyloid burden and neurodegeneration has recently been reported in a triple-transgenic AD (3xTg-AD) murine model. In the present study, we assessed the effect of scFv-h3D6, an anti-A beta single-chain variable fragment (scFv) derived from the antibody bapineuzumab, on amyloid pathology in 5-month-old 3xTg-AD female mice, focusing on intracellular A beta clearance, neuronal survival, and functional abilities. We also examined neuroinflammation and the histology of peripheral organ samples to detect any adverse effects. A single intraperitoneal injection of scFv-h3D6 dramatically reduced intracellular A beta burden in the deep layers of the cerebral cortex, pyramidal cells layer of the hippocampus, and basolateral amygdalar nucleus. The treatment prevented neuronal loss in the hippocampus and amygdala, while neither astrogliosis nor microgliosis was induced. Instead, an increase in the size of the white pulp after the treatment indicated that the spleen could be involved in the clearance mechanism. Although the treatment did not ameliorate behavioral and psychological symptoms of dementia-like symptoms, the results of cognitive testing pointed to a noticeable improvement in spatial memory. These findings indicated that the mechanism underlying the therapeutic effect of scFv-h3D6 was the clearance of intracellular A beta with subsequent prevention of neuronal loss and amelioration of cognitive disabilities. The treatment was safe in terms of neuroinflammation and kidney and liver function, whereas some effects on the spleen were observed.
Grants:	Instituto de Salud Carlos III FIS-PI113-01330 Agencia Estatal de Investigación SAF2017-89613
Note:	Generalitat de Catalunya (2014-PROD00032)
Rights:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	3xTg-AD ; Alzheimer's disease ; Amyloid-β ; Immunotherapy ; ScFv
Published in:	Journal of Alzheimer's disease, Vol. 70 Núm. 4 (2019) , p. 1069-1091, ISSN 1875-8908

DOI: 10.3233/JAD-190484
PMID: 31306135

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