| Autor: |
Dylan Garceau, Jennifer D. Whitesell, Julie A. Harris, Hilda Solanoy, Hoang Nguyen, Gilbert Di Paolo, Connie W.Y. Ha, Robert G. Thorne, Meredith E. K. Calvert, Joseph W. Lewcock, Karin Lin, Roni Chau, Thomas Sandmann, Sarah L. DeVos, Steve Lianoglou, Michael Sasner, Michelle E. Pizzo, Richard H. Liang, Jason C. Dugas, Jung H. Suh, Elliot R. Thomsen, Timothy K. Earr, Chia-Ching Lin, Kimberly Scearce-Levie, Dan Xia, Sonnet S. Davis, Shababa T. Masoud, Pascal E. Sanchez, Ernie Yulyaningsih |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Microglial dysfunction is believed to play a pathogenic role in Alzheimer’s disease (AD). Here, we characterize the amyloid-β 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 Aβ triggers lipid dysregulation and immuno-metabolic perturbations in phagocytic microglia.HighlightsNovel open-access APP KI mouse model shows salient AD pathological featuresDeep phenotyping of sorted microglia reveals profound lipidomic perturbations in line with Alois Alzheimer’s original descriptions of glial adipose inclusionsImmunometabolic perturbations are exacerbated in microglia accumulating fibrillar Aβ |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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