| First Author | Moelgg K | Year | 2021 |
| Journal | Biomolecules | Volume | 11 |
| Issue | 3 | PubMed ID | 33804246 |
| Mgi Jnum | J:348491 | Mgi Id | MGI:6808358 |
| Doi | 10.3390/biom11030434 | Citation | Moelgg K, et al. (2021) Spreading of Beta-Amyloid in Organotypic Mouse Brain Slices and Microglial Elimination and Effects on Cholinergic Neurons. Biomolecules 11(3) |
| abstractText | The extracellular deposition of beta-amyloid (Abeta) is one of the major characteristics in Alzheimer s disease (AD). The "spreading hypothesis" 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 8-10 mice. Using collagen hydrogels, we applied different Abeta peptides onto brain slices and analyzed spreading as well as glial reactions after eight weeks of incubation. Our data showed that from all tested Abeta peptides, human Abeta42 had the most potent activity to spread over into adjacent "target" areas. This effect was potentiated when brain slices from transgenic AD mice (APP_SweDI) were cultured. When different brain areas were connected to the "target slice" the spreading activity was more intense, originating from ventral striatum and brain stem. Reactive glial-fibrillary acidic protein (GFAP) astrogliosis increased over time, but Abeta depositions co-localized only with Iba1+ microglia but not with astrocytes. Application of human Abeta42 did not cause a degeneration of cholinergic neurons. We concluded that human Abeta42 spreads over into other "target areas", causing activation of glial cells. Most of the spread Abeta42 was taken up by microglia, and thus toxic free Abeta could not damage cholinergic neurons. |
