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Open Access 01-08-2013 | Original Paper

N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits

Authors: Yvonne Bouter, Katharina Dietrich, Jessica L. Wittnam, Nasrollah Rezaei-Ghaleh, Thierry Pillot, Sophie Papot-Couturier, Thomas Lefebvre, Frederick Sprenger, Oliver Wirths, Markus Zweckstetter, Thomas A. Bayer

Published in: Acta Neuropathologica | Issue 2/2013

Abstract

N-truncated Aβ_4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ_4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ_4-42 is as toxic as pyroglutamate Aβ_3-42 and Aβ_1-42. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ_4-42, pyroglutamate Aβ_3-42 and Aβ_1-42. Transgenic mice expressing Aβ_4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ_4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N-truncated Aβ_4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.

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Title: N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits
Authors: Yvonne Bouter
Katharina Dietrich
Jessica L. Wittnam
Nasrollah Rezaei-Ghaleh
Thierry Pillot
Sophie Papot-Couturier
Thomas Lefebvre
Frederick Sprenger
Oliver Wirths
Markus Zweckstetter
Thomas A. Bayer
Publication date: 01-08-2013
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 2/2013
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-013-1129-2

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N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits

Abstract

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