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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

N-truncated Aβ4–x peptides in sporadic Alzheimer’s disease cases and transgenic Alzheimer mouse models

Authors: Oliver Wirths, Susanne Walter, Inga Kraus, Hans W. Klafki, Martina Stazi, Timo J. Oberstein, Jorge Ghiso, Jens Wiltfang, Thomas A. Bayer, Sascha Weggen

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

Background

The deposition of neurotoxic amyloid-β (Aβ) peptides in plaques in the brain parenchyma and in cerebral blood vessels is considered to be a key event in Alzheimer’s disease (AD) pathogenesis. Although the presence and impact of full-length Aβ peptides such as Aβ1–40 and Aβ1–42 have been analyzed extensively, the deposition of N-terminally truncated Aβ peptide species has received much less attention, largely because of the lack of specific antibodies.

Methods

This paper describes the generation and characterization of novel antibodies selective for Aβ4–x peptides and provides immunohistochemical evidence of Aβ4–x in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models.

Results

The Aβ4–x staining pattern was restricted mainly to amyloid plaque cores and cerebral amyloid angiopathy in AD and Down syndrome cases and in both AD mouse models. In contrast, diffuse amyloid deposits were largely negative for Aβ4–x immunoreactivity. No overt intraneuronal staining was observed.

Conclusions

The findings of this study are consistent with previous reports demonstrating a high aggregation propensity of Aβ4–x peptides and suggest an important role of these N-truncated Aβ species in the process of amyloidogenesis and plaque core formation.
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Metadata
Title
N-truncated Aβ4–x peptides in sporadic Alzheimer’s disease cases and transgenic Alzheimer mouse models
Authors
Oliver Wirths
Susanne Walter
Inga Kraus
Hans W. Klafki
Martina Stazi
Timo J. Oberstein
Jorge Ghiso
Jens Wiltfang
Thomas A. Bayer
Sascha Weggen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0309-z

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