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

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.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-31E6-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-6DF1-B
Genre: Journal Article

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http://www.nature.com/articles/srep17338.pdf (Publisher version)
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 Creators:
Antonios, G., Author
Borgers, H., Author
Richard, B. C., Author
Brauss, A, Author
Meissner, J., Author
Weggen, S., Author
Pena, V.1, Author              
Pillot, T., Author
Davies, S. T., Author
Bakrania, P., Author
Matthews, D., Author
Brownlees, J., Author
Bouter, Y., Author
Bayer, T. A, Author
Affiliations:
1Research Group of Macromolecular Crystallography, MPI for Biophysical Chemistry, Max Planck Society, ou_2035293              

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 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.

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Language(s): eng - English
 Dates: 2015-12-02
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/srep17338
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Title: Scientific Reports
Source Genre: Journal
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Pages: 14 Volume / Issue: 5 Sequence Number: 17338 Start / End Page: - Identifier: -