title: Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice.
abstract: We screened anti-Aβ1-42 antibodies from a human Alzheimer's disease (AD) specific single chain variable fragment (scFv) phage display library and assessed their effects in APP/PS1 transgenic mice. Reverse transcription-PCR was used to construct the scFv phage display library, and screening identified 11A5 as an anti-Aβ1-42 antibody. We mixed 11A5 and the monoclonal antibody 6E10 with Aβ1-42 and administered the mixture to Sprague-Dawley rats via intracerebroventricular injection. After 30 days, rats injected with the antibody/Aβ1-42 mixture and those injected with Aβ1-42 alone were tested on the Morris water maze. We also injected 11A5 and 6E10 into APP/PS1 transgenic mice and assessed the concentrations of Aβ in brain and peripheral blood by ELISA at 1-month intervals for 3 months. Finally we evaluated behavior changes in the Morris water maze. Rats injected with Aβ1-42 and mixed antibodies showed better performance in the Morris water maze than did rats injected with Aβ1-42 alone. In APP/PS1 transgenic mice, Aβ concentration was lower in the brains of the antibody-treated group than in the control group, but higher in the peripheral blood. The antibody-treated mice also exhibited improved behavioral performance in the Morris water maze. In conclusion, anti-Aβ1-42 antibodies (11A5) screened from the human scFv antibody phage display library promoted the efflux or clearance of Aβ1-42 and effectively decreased the cerebral Aβ burden in an AD mouse model.
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: wjpwfy666@126.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Electronic address: jwang79@jhmi.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology* / Q000633:toxicity*; D019151:Peptide Library; D053764:Presenilin-1 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D019151:Peptide Library; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42)
keywords: APP/PS1 transgenic mice; Alzheimer׳s disease; Anti-Aβ antibodies; Phage display library
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