| First Author | Xia D | Year | 2021 |
| Journal | bioRxiv | Mgi Jnum | J:299724 |
| Mgi Id | MGI:6501573 | Doi | 10.1101/2021.01.19.426731 |
| Citation | Xia D, et al. (2021) Fibrillar Abeta causes profound microglial metabolic perturbations in a novel APP knock-in mouse model. bioRxiv |
| abstractText | Microglial dysfunction is believed to play a pathogenic role in Alzheimerâs disease (AD). Here, we characterize the amyloid-b related pathology and microglial responses in an engineered APP knock-in mouse model of familial AD. This model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered glial responses and neurodegeneration. Leveraging multi-omics approaches, we found lipid accumulation and an exacerbated disease-associated transcriptomic response in methoxy-X04-positive, phagocytic microglia. Together, these findings highlight the potential of this novel, open-access mouse model to investigate AD pathogenesis and demonstrate that fibrillar Ab triggers lipid dysregulation and immuno-metabolic perturbations in phagocytic microglia. |
