| First Author | Rivera-Escalera F | Year | 2014 |
| Journal | Neurobiol Dis | Volume | 69 |
| Pages | 124-33 | PubMed ID | 24874542 |
| Mgi Jnum | J:259427 | Mgi Id | MGI:6141321 |
| Doi | 10.1016/j.nbd.2014.05.018 | Citation | Rivera-Escalera F, et al. (2014) Interleukin-1beta mediated amyloid plaque clearance is independent of CCR2 signaling in the APP/PS1 mouse model of Alzheimer's disease. Neurobiol Dis 69:124-33 |
| abstractText | Neuroinflammation is a key component of Alzheimer''s disease (AD) pathogenesis. Particularly, the proinflammatory cytokine interleukin-1 beta (IL-1beta) is upregulated in human AD and believed to promote amyloid plaque deposition. However, studies from our laboratory have shown that chronic IL-1beta overexpression in the APPswe/PSEN1dE9 (APP/PS1) mouse model of AD ameliorates amyloid pathology, increases plaque-associated microglia, and induces recruitment of peripheral immune cells to the brain parenchyma. To investigate the contribution of CCR2 signaling in IL-1beta-mediated amyloid plaque clearance, seven month-old APP/PS1/CCR2(-/-) mice were intrahippocampally transduced with a recombinant adeno-associated virus serotype 2 containing the cleaved form of human IL-1beta (rAAV2-IL-1beta). Four weeks after rAAV2-IL-1beta transduction, we found significant reductions in 6E10 and Congo red staining of amyloid plaques that was confirmed by decreased levels of insoluble Abeta1-42 and Abeta1-40 in the inflamed hippocampus. Bone marrow chimeric studies confirmed the presence of infiltrating immune cells following IL-1beta overexpression and revealed that dramatic reduction of CCR2(+) peripheral mononuclear cell recruitment to the inflamed hippocampus did not prevent the ability of IL-1beta to induce amyloid plaque clearance. These results suggest that infiltrating CCR2(+) monocytes do not contribute to IL-1beta-mediated amyloid plaque clearance. |
