Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases
The presence of AβpE3 (N-terminal truncated Aβ starting with pyroglutamate) in Alzheimer’s disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Aβ peptides in senile plaques of AD brains. This was later confirmed by other reports in...
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ftpubmed:oai:pubmedcentral.nih.gov:2789212 2023-05-15T15:10:36+02:00 Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases Wirths, Oliver Bethge, Tobias Marcello, Andrea Harmeier, Anja Jawhar, Sadim Lucassen, Paul J. Multhaup, Gerd Brody, David L. Esparza, Thomas Ingelsson, Martin Kalimo, Hannu Lannfelt, Lars Bayer, Thomas A. 2009-10-13 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789212 http://www.ncbi.nlm.nih.gov/pubmed/19823761 https://doi.org/10.1007/s00702-009-0314-x en eng Springer Vienna http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789212 http://www.ncbi.nlm.nih.gov/pubmed/19823761 http://dx.doi.org/10.1007/s00702-009-0314-x © The Author(s) 2009 Dementias - Original Article Text 2009 ftpubmed https://doi.org/10.1007/s00702-009-0314-x 2013-09-02T19:33:25Z The presence of AβpE3 (N-terminal truncated Aβ starting with pyroglutamate) in Alzheimer’s disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Aβ peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down’s syndrome postmortem brain tissue. Importantly, AβpE3 has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Aβ. We have recently shown that intraneuronal accumulation of AβpE3 peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in AβpE3, we have generated two novel monoclonal antibodies which were characterized as highly specific for AβpE3 peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for AβpE3 were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in AβpE3 plaque load with increasing age, while the density for Aβ1-x plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Aβ are N-truncated as disease progresses, and that, AβpE3 positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate. Text Arctic PubMed Central (PMC) Arctic Journal of Neural Transmission 117 1 85 96 |
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Dementias - Original Article |
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Dementias - Original Article Wirths, Oliver Bethge, Tobias Marcello, Andrea Harmeier, Anja Jawhar, Sadim Lucassen, Paul J. Multhaup, Gerd Brody, David L. Esparza, Thomas Ingelsson, Martin Kalimo, Hannu Lannfelt, Lars Bayer, Thomas A. Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases |
topic_facet |
Dementias - Original Article |
description |
The presence of AβpE3 (N-terminal truncated Aβ starting with pyroglutamate) in Alzheimer’s disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Aβ peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down’s syndrome postmortem brain tissue. Importantly, AβpE3 has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Aβ. We have recently shown that intraneuronal accumulation of AβpE3 peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in AβpE3, we have generated two novel monoclonal antibodies which were characterized as highly specific for AβpE3 peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for AβpE3 were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in AβpE3 plaque load with increasing age, while the density for Aβ1-x plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Aβ are N-truncated as disease progresses, and that, AβpE3 positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate. |
format |
Text |
author |
Wirths, Oliver Bethge, Tobias Marcello, Andrea Harmeier, Anja Jawhar, Sadim Lucassen, Paul J. Multhaup, Gerd Brody, David L. Esparza, Thomas Ingelsson, Martin Kalimo, Hannu Lannfelt, Lars Bayer, Thomas A. |
author_facet |
Wirths, Oliver Bethge, Tobias Marcello, Andrea Harmeier, Anja Jawhar, Sadim Lucassen, Paul J. Multhaup, Gerd Brody, David L. Esparza, Thomas Ingelsson, Martin Kalimo, Hannu Lannfelt, Lars Bayer, Thomas A. |
author_sort |
Wirths, Oliver |
title |
Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases |
title_short |
Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases |
title_full |
Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases |
title_fullStr |
Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases |
title_full_unstemmed |
Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases |
title_sort |
pyroglutamate abeta pathology in app/ps1ki mice, sporadic and familial alzheimer’s disease cases |
publisher |
Springer Vienna |
publishDate |
2009 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789212 http://www.ncbi.nlm.nih.gov/pubmed/19823761 https://doi.org/10.1007/s00702-009-0314-x |
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Arctic |
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Arctic |
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Arctic |
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Arctic |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789212 http://www.ncbi.nlm.nih.gov/pubmed/19823761 http://dx.doi.org/10.1007/s00702-009-0314-x |
op_rights |
© The Author(s) 2009 |
op_doi |
https://doi.org/10.1007/s00702-009-0314-x |
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Journal of Neural Transmission |
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117 |
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1 |
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85 |
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96 |
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1766341591052582912 |