| First Author | Kiyota T | Year | 2013 |
| Journal | Neurobiol Aging | Volume | 34 |
| Issue | 4 | Pages | 1060-8 |
| PubMed ID | 23040664 | Mgi Jnum | J:203385 |
| Mgi Id | MGI:5526916 | Doi | 10.1016/j.neurobiolaging.2012.08.009 |
| Citation | Kiyota T, et al. (2013) CCL2 affects beta-amyloidosis and progressive neurocognitive dysfunction in a mouse model of Alzheimer's disease. Neurobiol Aging 34(4):1060-8 |
| abstractText | Neuroinflammation affects the pathobiology of Alzheimer's disease (AD). Notably, beta-amyloid (Abeta) deposition induces microglial activation and the subsequent production of proinflammatory neurotoxic factors. In maintaining brain homeostasis, microglial plasticity also enables phenotypic transition between toxic and trophic activation states. One important control for such cell activation is through the CC-chemokine ligand 2 (CCL2) and its receptor, the CC-chemokine receptor 2. Both affect microglia and peripheral macrophage immune responses and for the latter, cell ingress across the blood-brain barrier. However, how CCL2-CC-chemokine receptor 2 signaling contributes to AD pathogenesis is not well understood. To this end, we now report that CCL2 deficiency influences behavioral abnormalities and disease progression in Abeta precursor protein/presenilin-1 double-transgenic mice. Here, increased cortical and hippocampal Abeta deposition is coincident with the formulation of Abeta oligomers. Deficits in peripheral Abeta clearance and in scavenger, neuroprogenitor, and microglial cell functions are linked to deficient Abeta uptake. All serve to accelerate memory dysfunction. Taken together, these data support a role of CCL2 in innate immune functions relevant to AD pathogenesis. |
