Microglia contribute to the propagation of Aβ into unaffected brain tissue

Microglia appear activated in the vicinity of amyloid beta (Aβ) plaques, but whether microglia contribute to Aβ propagation into unaffected brain regions remains unknown. Using transplantation of wild-type (WT) neurons, we show that Aβ enters WT grafts, and that this is accompanied by microglia infi...

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Veröffentlicht in:Nature neuroscience 2022-01, Vol.25 (1), p.20-25
Hauptverfasser: d’Errico, Paolo, Ziegler-Waldkirch, Stephanie, Aires, Vanessa, Hoffmann, Philippe, Mezö, Charlotte, Erny, Daniel, Monasor, Laura Sebastian, Liebscher, Sabine, Ravi, Vidhya M., Joseph, Kevin, Schnell, Oliver, Kierdorf, Katrin, Staszewski, Ori, Tahirovic, Sabina, Prinz, Marco, Meyer-Luehmann, Melanie
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Sprache:eng
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Zusammenfassung:Microglia appear activated in the vicinity of amyloid beta (Aβ) plaques, but whether microglia contribute to Aβ propagation into unaffected brain regions remains unknown. Using transplantation of wild-type (WT) neurons, we show that Aβ enters WT grafts, and that this is accompanied by microglia infiltration. Manipulation of microglia function reduced Aβ deposition within grafts. Furthermore, in vivo imaging identified microglia as carriers of Aβ pathology in previously unaffected tissue. Our data thus argue for a hitherto unexplored mechanism of Aβ propagation. This study shows that Aβ from transgenic host tissue is able to enter and deposit within wild-type grafts via microglia, thus identifying microglia as carriers of Aβ deposition into previously unaffected brain tissue.
ISSN:1097-6256
1546-1726
DOI:10.1038/s41593-021-00951-0