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Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease
Neuropathologically, Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-beta peptide (Aβ) and subsequent formation of the so-called Aβ plaques. Along with neuronal loss, previous studies report white matter anomalies and corpus callosum (CC) atrophy in AD patients. Notably, per...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393256/ https://www.ncbi.nlm.nih.gov/pubmed/36003141 http://dx.doi.org/10.3389/fncel.2022.862918 |
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author | Aires, Vanessa Ziegler-Waldkirch, Stephanie Friesen, Marina Reichardt, Wilfried Erny, Daniel Loreth, Desiree Harborne, Andrew Kretz, Oliver von Elverfeldt, Dominik Meyer-Luehmann, Melanie |
author_facet | Aires, Vanessa Ziegler-Waldkirch, Stephanie Friesen, Marina Reichardt, Wilfried Erny, Daniel Loreth, Desiree Harborne, Andrew Kretz, Oliver von Elverfeldt, Dominik Meyer-Luehmann, Melanie |
author_sort | Aires, Vanessa |
collection | PubMed |
description | Neuropathologically, Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-beta peptide (Aβ) and subsequent formation of the so-called Aβ plaques. Along with neuronal loss, previous studies report white matter anomalies and corpus callosum (CC) atrophy in AD patients. Notably, perturbations in the white matter can be observed years before expected disease onset, suggesting that early stages of disease progression play a role in AD-associated loss of myelin integrity. Through seed-induced deposition of Aβ, we are able to examine alterations of central nervous system (CNS) integrity during the initial stages of plaque formation. In this study, we investigate the impact of Aβ seeding in the CC utilizing various imaging techniques as well as quantitative gene expression analysis and demonstrate that Aβ deposits result in an imbalance of glial cells in the CC. We found increased amounts of phagocytic microglia and reactive astrocytes, while oligodendrocyte progenitor cell (OPC) numbers were reduced. Moreover, white matter aberrations adjacent to the Aβ seeding were observed together with an overall decline in callosal myelination. This data indicate that the initial stages of plaque formation induce oligodendrocyte dysfunction, which might ultimately lead to myelin loss. |
format | Online Article Text |
id | pubmed-9393256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93932562022-08-23 Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease Aires, Vanessa Ziegler-Waldkirch, Stephanie Friesen, Marina Reichardt, Wilfried Erny, Daniel Loreth, Desiree Harborne, Andrew Kretz, Oliver von Elverfeldt, Dominik Meyer-Luehmann, Melanie Front Cell Neurosci Neuroscience Neuropathologically, Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-beta peptide (Aβ) and subsequent formation of the so-called Aβ plaques. Along with neuronal loss, previous studies report white matter anomalies and corpus callosum (CC) atrophy in AD patients. Notably, perturbations in the white matter can be observed years before expected disease onset, suggesting that early stages of disease progression play a role in AD-associated loss of myelin integrity. Through seed-induced deposition of Aβ, we are able to examine alterations of central nervous system (CNS) integrity during the initial stages of plaque formation. In this study, we investigate the impact of Aβ seeding in the CC utilizing various imaging techniques as well as quantitative gene expression analysis and demonstrate that Aβ deposits result in an imbalance of glial cells in the CC. We found increased amounts of phagocytic microglia and reactive astrocytes, while oligodendrocyte progenitor cell (OPC) numbers were reduced. Moreover, white matter aberrations adjacent to the Aβ seeding were observed together with an overall decline in callosal myelination. This data indicate that the initial stages of plaque formation induce oligodendrocyte dysfunction, which might ultimately lead to myelin loss. Frontiers Media S.A. 2022-08-08 /pmc/articles/PMC9393256/ /pubmed/36003141 http://dx.doi.org/10.3389/fncel.2022.862918 Text en Copyright © 2022 Aires, Ziegler-Waldkirch, Friesen, Reichardt, Erny, Loreth, Harborne, Kretz, von Elverfeldt and Meyer-Luehmann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Aires, Vanessa Ziegler-Waldkirch, Stephanie Friesen, Marina Reichardt, Wilfried Erny, Daniel Loreth, Desiree Harborne, Andrew Kretz, Oliver von Elverfeldt, Dominik Meyer-Luehmann, Melanie Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease |
title | Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease |
title_full | Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease |
title_fullStr | Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease |
title_full_unstemmed | Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease |
title_short | Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease |
title_sort | seed-induced aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of alzheimer’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393256/ https://www.ncbi.nlm.nih.gov/pubmed/36003141 http://dx.doi.org/10.3389/fncel.2022.862918 |
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