Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice

We screened anti-A beta 1-42 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-A beta 1-42 antibody. We mixed 11A5 and the monoclonal antibody 6E10 with A beta 1-42 and administered the mixture to Sprague-Dawley rats via intracerebroventricular injection. After 30 days, rats injected with the antibody/A beta 1-42 mixture and those injected with A beta 1-42 alone were tested on the Morris water maze. We also injected 11A5 and 6E10 into APP/PS1 transgenic mice and assessed the concentrations of All 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 A beta 1-42 and mixed antibodies showed better performance in the Morris water maze than did rats injected with A beta 1-42 alone. In APP/P51 transgenic mice, Ala 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-A beta 1-42 antibodies (11A5) screened from the human scFv antibody phage display library promoted the efflux or clearance of A beta 1-42 and effectively decreased the cerebral A beta burden in an AD mouse model. (C) 2016 Elsevier B.V. All rights reserved.