{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:01:29Z","timestamp":1769598089951,"version":"3.49.0"},"reference-count":68,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P32558-B"],"award-info":[{"award-number":["P32558-B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The extracellular deposition of \u03b2-amyloid (A\u03b2) is one of the major characteristics in Alzheimer\u00b4s disease (AD). The \u201cspreading hypothesis\u201d suggests that a pathological protein (similar to prions) spreads over the entire brain. The aim of the present study was to use organotypic brain slices of postnatal day 8\u201310 mice. Using collagen hydrogels, we applied different A\u03b2 peptides onto brain slices and analyzed spreading as well as glial reactions after eight weeks of incubation. Our data showed that from all tested A\u03b2 peptides, human A\u03b242 had the most potent activity to spread over into adjacent \u201ctarget\u201d areas. This effect was potentiated when brain slices from transgenic AD mice (APP_SweDI) were cultured. When different brain areas were connected to the \u201ctarget slice\u201d the spreading activity was more intense, originating from ventral striatum and brain stem. Reactive glial-fibrillary acidic protein (GFAP) astrogliosis increased over time, but A\u03b2 depositions co-localized only with Iba1+ microglia but not with astrocytes. Application of human A\u03b242 did not cause a degeneration of cholinergic neurons. We concluded that human A\u03b242 spreads over into other \u201ctarget areas\u201d, causing activation of glial cells. Most of the spread A\u03b242 was taken up by microglia, and thus toxic free A\u03b2 could not damage cholinergic neurons.<\/jats:p>","DOI":"10.3390\/biom11030434","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T22:16:54Z","timestamp":1615846614000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Spreading of Beta-Amyloid in Organotypic Mouse Brain Slices and Microglial Elimination and Effects on Cholinergic Neurons"],"prefix":"10.3390","volume":"11","author":[{"given":"Kurt","family":"Moelgg","sequence":"first","affiliation":[{"name":"Laboratory of Psychiatry and Experimental Alzheimer\u2019s Research, Department Psychiatry I, Medical University of Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faryal","family":"Jummun","sequence":"additional","affiliation":[{"name":"Laboratory of Psychiatry and Experimental Alzheimer\u2019s Research, Department Psychiatry I, Medical University of Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Humpel","sequence":"additional","affiliation":[{"name":"Laboratory of Psychiatry and Experimental Alzheimer\u2019s Research, Department Psychiatry I, Medical University of Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1365-2990.2010.01137.x","article-title":"Review: Sporadic cerebral amyloid angiopathy","volume":"37","author":"Attems","year":"2011","journal-title":"Neuropathol. 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