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N-truncated A?4-x peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models.

ABSTRACT: The deposition of neurotoxic amyloid-? (A?) 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 A? peptides such as A?1-40 and A?1-42 have been analyzed extensively, the deposition of N-terminally truncated A? peptide species has received much less attention, largely because of the lack of specific antibodies.This paper describes the generation and characterization of novel antibodies selective for A?4-x peptides and provides immunohistochemical evidence of A?4-x in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models.The A?4-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 A?4-x immunoreactivity. No overt intraneuronal staining was observed.The findings of this study are consistent with previous reports demonstrating a high aggregation propensity of A?4-x peptides and suggest an important role of these N-truncated A? species in the process of amyloidogenesis and plaque core formation.

SUBMITTER: Wirths O

PROVIDER: S-EPMC5628465 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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N-truncated Aβ<sub>4-x</sub> peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models.

Wirths Oliver O Walter Susanne S Kraus Inga I Klafki Hans W HW Stazi Martina M Oberstein Timo J TJ Ghiso Jorge J Wiltfang Jens J Bayer Thomas A TA Weggen Sascha S

Alzheimer's research & therapy 20171004 1

<h4>Background</h4>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 Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub> 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.<h4> ...[more]

PMID: 28978359

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Dataset Information

N-truncated A?4-x peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models.

Publications

N-truncated Aβ<sub>4-x</sub> peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models.

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