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Journal Article

Alzheimer therapy with an antibody against N-terminal Abeta 4-X and pyroglutamate Abeta 3-X.

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Pena,  V.
Research Group of Macromolecular Crystallography, MPI for Biophysical Chemistry, Max Planck Society;

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Citation

Antonios, G., Borgers, H., Richard, B. C., Brauss, A., Meissner, J., Weggen, S., et al. (2015). Alzheimer therapy with an antibody against N-terminal Abeta 4-X and pyroglutamate Abeta 3-X. Scientific Reports, 5: 17338. doi:10.1038/srep17338.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0029-31E6-1
Abstract
Full-length A beta 1-42 and A beta 1-40, N-truncated pyroglutamate A beta 3-42 and A beta 4-42 are major variants in the Alzheimer brain. A beta 4-42 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 A beta 4-x and pyroglutamate A beta 3-X mitigated neuron loss in Tg4-42 mice expressing A beta 4-42 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 A beta 4-42. NT4X reduced pyroglutamate A beta 3-x, A beta x-40 and Thioflavin-S positive plaque load after passive immunization of 5XFAD mice. A beta 1-x and A beta x-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 A beta starting with position four in addition to pyroglutamate A beta 3-x is a relevant target to fight Alzheimer's disease.