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Publication : Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-β plaque formation in organotypic hippocampal slice cultures.

First Author  Hellwig S Year  2015
Journal  Sci Rep Volume  5
Pages  14624 PubMed ID  26416689
Mgi Jnum  J:361207 Mgi Id  MGI:6217193
Doi  10.1038/srep14624 Citation  Hellwig S, et al. (2015) Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-beta plaque formation in organotypic hippocampal slice cultures. Sci Rep 5:14624
abstractText  The role of microglia in amyloid-beta (Abeta) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to Abeta plaque formation. We found that microglia ingested Abeta, thereby preventing plaque formation in OHSCs. Conversely, Abeta deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent Abeta plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer's disease (FAD) mice. Since no loss of Abeta clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high Abeta1-42 burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial Abeta clearance capacity. These data may therefore explain why Abeta plaque formation has never been described in wild-type mice, and point to a beneficial role of microglia in AD pathology. We also describe a new method to study Abeta plaque formation in a cell culture setting.
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