| First Author | Baligács N | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 10634 |
| PubMed ID | 39639016 | Mgi Jnum | J:361232 |
| Mgi Id | MGI:7787678 | Doi | 10.1038/s41467-024-54779-w |
| Citation | Baligacs N, et al. (2024) Homeostatic microglia initially seed and activated microglia later reshape amyloid plaques in Alzheimer's Disease. Nat Commun 15(1):10634 |
| abstractText | The role of microglia in the amyloid cascade of Alzheimer's disease (AD) is debated due to conflicting findings. Using a genetic and a pharmacological approach we demonstrate that depletion of microglia before amyloid-beta (Abeta) plaque deposition, leads to a reduction in plaque numbers and neuritic dystrophy, confirming their role in plaque initiation. Transplanting human microglia restores Abeta plaque formation. While microglia depletion reduces insoluble Abeta levels, soluble Abeta concentrations stay consistent, challenging the view that microglia clear Abeta. In later stages, microglial depletion decreases plaque compaction and increases neuritic dystrophy, suggesting a protective role. Human microglia with the TREM2(R47H/R47H) mutation exacerbate plaque pathology, emphasizing the importance of non-reactive microglia in the initiation of the amyloid cascade. Adaptive immune depletion (Rag2(-/-)) does not affect microglia's impact on plaque formation. These findings clarify conflicting reports, identifying microglia as key drivers of amyloid pathology, and raise questions about optimal therapeutic strategies for AD. |
