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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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 Urheber:
Antonios, G., Autor
Borgers, H., Autor
Richard, B. C., Autor
Brauss, A, Autor
Meissner, J., Autor
Weggen, S., Autor
Pena, V.1, Autor           
Pillot, T., Autor
Davies, S. T., Autor
Bakrania, P., Autor
Matthews, D., Autor
Brownlees, J., Autor
Bouter, Y., Autor
Bayer, T. A, Autor
Affiliations:
1Research Group of Macromolecular Crystallography, MPI for Biophysical Chemistry, Max Planck Society, ou_2035293              

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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2015-12-02
 Publikationsstatus: Online veröffentlicht
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/srep17338
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Titel: Scientific Reports
Genre der Quelle: Zeitschrift
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Seiten: 14 Band / Heft: 5 Artikelnummer: 17338 Start- / Endseite: - Identifikator: -