An anti-pyroglutamate-3 A? vaccine reduces plaques and improves cognition in APPswe/PS1?E9 mice.

ABSTRACT: Pyroglutamate-3 amyloid-beta (pGlu-3 A?) is an N-terminally truncated A? isoform likely playing a decisive role in Alzheimer's disease pathogenesis. Here, we describe a prophylactic passive immunization study in APPswe/PS1?E9 mice using a novel pGlu-3 A? immunoglobulin G1 (IgG1) monoclonal antibody, 07/1 (150 and 500 ?g, intraperitoneal, weekly) and compare its efficacy with a general A? IgG1 monoclonal antibody, 3A1 (200 ?g, intraperitoneal, weekly) as a positive control. After 28 weeks of treatment, plaque burden was reduced and cognitive performance of 07/1-immunized Tg mice, especially at the higher dose, was normalized to wild-type levels in 2 hippocampal-dependent tests and partially spared compared with phosphate-buffered saline-treated Tg mice. Mice that received 3A1 had reduced plaque burden but showed no cognitive benefit. In contrast with 3A1, treatment with 07/1 did not increase the concentration of A? in plasma, suggesting different modes of A? plaque clearance. In conclusion, early selective targeting of pGlu-3 A? by immunotherapy may be effective in lowering cerebral A? plaque burden and preventing cognitive decline in the clinical setting. Targeting this pathologically modified form of A? thereby is unlikely to interfere with potential physiologic function(s) of A? that have been proposed.

SUBMITTER: Frost JL 

PROVIDER: S-EPMC4641825 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature