| First Author | Frost JL | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 12 | Pages | 3187-3199 |
| PubMed ID | 26453001 | Mgi Jnum | J:232371 |
| Mgi Id | MGI:5776667 | Doi | 10.1016/j.neurobiolaging.2015.08.021 |
| Citation | Frost JL, et al. (2015) An anti-pyroglutamate-3 Abeta vaccine reduces plaques and improves cognition in APPswe/PS1DeltaE9 mice. Neurobiol Aging 36(12):3187-3199 |
| abstractText | Pyroglutamate-3 amyloid-beta (pGlu-3 Abeta) is an N-terminally truncated Abeta isoform likely playing a decisive role in Alzheimer's disease pathogenesis. Here, we describe a prophylactic passive immunization study in APPswe/PS1DeltaE9 mice using a novel pGlu-3 Abeta immunoglobulin G1 (IgG1) monoclonal antibody, 07/1 (150 and 500 mug, intraperitoneal, weekly) and compare its efficacy with a general Abeta IgG1 monoclonal antibody, 3A1 (200 mug, 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 Abeta in plasma, suggesting different modes of Abeta plaque clearance. In conclusion, early selective targeting of pGlu-3 Abeta by immunotherapy may be effective in lowering cerebral Abeta plaque burden and preventing cognitive decline in the clinical setting. Targeting this pathologically modified form of Abeta thereby is unlikely to interfere with potential physiologic function(s) of Abeta that have been proposed. |
