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Cell. Neurosci."],"abstract":"<jats:p>Neuropathologically, Alzheimer\u2019s disease (AD) is characterized by the accumulation of amyloid-beta peptide (A\u03b2) and subsequent formation of the so-called A\u03b2 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 A\u03b2, 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 A\u03b2 seeding in the CC utilizing various imaging techniques as well as quantitative gene expression analysis and demonstrate that A\u03b2 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 A\u03b2 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.<\/jats:p>","DOI":"10.3389\/fncel.2022.862918","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T05:07:26Z","timestamp":1659935246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Seed-induced A\u03b2 deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Vanessa","family":"Aires","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Ziegler-Waldkirch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Friesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Reichardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Erny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree","family":"Loreth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Harborne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Kretz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"von Elverfeldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Meyer-Luehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1038\/nm.3885","article-title":"Inhibition of amyloid-\u03b2 plaque formation by \u03b1-synuclein.","volume":"21","author":"Bachhuber","year":"2015","journal-title":"Nat. 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