| First Author | Antonios G | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 17338 | PubMed ID | 26626428 |
| Mgi Jnum | J:284812 | Mgi Id | MGI:6220016 |
| Doi | 10.1038/srep17338 | Citation | Antonios G, et al. (2015) Alzheimer therapy with an antibody against N-terminal Abeta 4-X and pyroglutamate Abeta 3-X. Sci Rep 5:17338 |
| abstractText | Full-length Abeta1-42 and Abeta1-40, N-truncated pyroglutamate Abeta3-42 and Abeta4-42 are major variants in the Alzheimer brain. Abeta4-42 has not been considered as a therapeutic target yet. We demonstrate that the antibody NT4X and its Fab fragment reacting with both the free N-terminus of Abeta4-x and pyroglutamate Abeta3-X mitigated neuron loss in Tg4-42 mice expressing Abeta4-42 and completely rescued spatial reference memory deficits after passive immunization. NT4X and its Fab fragment also rescued working memory deficits in wild type mice induced by intraventricular injection of Abeta4-42. NT4X reduced pyroglutamate Abeta3-x, Abetax-40 and Thioflavin-S positive plaque load after passive immunization of 5XFAD mice. Abeta1-x and Abetax-42 plaque deposits were unchanged. Importantly, for the first time, we demonstrate that passive immunization using the antibody NT4X is therapeutically beneficial in Alzheimer mouse models showing that N-truncated Abeta starting with position four in addition to pyroglutamate Abeta3-x is a relevant target to fight Alzheimer''s disease. |
