| First Author | Baik SH | Year | 2016 |
| Journal | Glia | Volume | 64 |
| Issue | 12 | Pages | 2274-2290 |
| PubMed ID | 27658617 | Mgi Jnum | J:236228 |
| Mgi Id | MGI:5805566 | Doi | 10.1002/glia.23074 |
| Citation | Baik SH, et al. (2016) Microglia contributes to plaque growth by cell death due to uptake of amyloid beta in the brain of Alzheimer's disease mouse model. Glia 64(12):2274-2290 |
| abstractText | Pathological hallmarks of Alzheimer's disease (AD) include extracellularly accumulated amyloid beta (Abeta) plaques and intracellular neurofibrillary tangles in the brain. Activated microglia, brain-resident macrophages, are also found surrounding Abeta plaques. The study of the brain of AD mouse models revealed that Abeta plaque formation is completed by the consolidation of newly generated plaque clusters in vicinity of existed plaques. However, the dynamics of Abeta plaque formation, growth and the mechanisms by which microglia contribute to Abeta plaque formation are unknown. In the present study, we confirmed how microglia are involved in Abeta plaque formation and their growth in the brain of 5XFAD mice, the Abeta-overexpressing AD transgenic mouse model, and performed serial intravital two-photon microscopy (TPM) imaging of the brains of 5XFAD mice crossed with macrophage/microglia-specific GFP-expressing CX3CR1GFP/GFP mice. We found that activated microglia surrounding Abeta plaques take up Abeta, which are clusters developed inside activated microglia in vivo and this was followed by microglial cell death. These dying microglia release the accumulated Abeta into the extracellular space, which contributes to Abeta plaque growth. This process was confirmed by live TPM in vivo imaging and flow cytometry. These results suggest that activated microglia can contribute to formation and growth of Abeta plaques by causing microglial cell death in the brain. GLIA 2016;64:2274-2290. |
