Aires, Vanessa and Ziegler-Waldkirch, Stephanie and Friesen, Marina and Reichardt, Wilfried and Erny, Daniel and Loreth, Desiree and Harborne, Andrew and Kretz, Oliver and von Elverfeldt, Dominik and Meyer-Luehmann, Melanie (2022) Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer’s disease. Frontiers in Cellular Neuroscience, 16. ISSN 1662-5102
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Abstract
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.
Item Type: | Article |
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Subjects: | EP Archives > Medical Science |
Depositing User: | Managing Editor |
Date Deposited: | 29 Mar 2023 05:02 |
Last Modified: | 05 Feb 2024 04:40 |
URI: | http://research.send4journal.com/id/eprint/1799 |