| First Author | Ghosh S | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 11 | Pages | 5053-64 |
| PubMed ID | 23486975 | Mgi Jnum | J:196598 |
| Mgi Id | MGI:5488847 | Doi | 10.1523/JNEUROSCI.4361-12.2013 |
| Citation | Ghosh S, et al. (2013) Sustained interleukin-1beta overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer's mouse model. J Neurosci 33(11):5053-64 |
| abstractText | Neuroinflammation is an important component of Alzheimer's disease (AD) pathogenesis and has been implicated in neurodegeneration. Interleukin-1 (IL-1), a potent inflammatory cytokine in the CNS, is chronically upregulated in human AD and believed to serve as part of a vicious inflammatory cycle that drives AD pathology. To further understand the role of IL-1beta in AD pathogenesis, we used an inducible model of sustained IL-1beta overexpression (IL-1beta(XAT)) developed in our laboratory. The triple transgenic mouse model of AD, which develops plaques and tangles later in its life cycle, was bred with IL-1beta(XAT) mice, and effects of IL-1beta overexpression on AD pathology were assessed in F1 progeny. After 1 and 3 months of transgene expression, we found robust increases in tau phosphorylation despite an approximately 70-80% reduction in amyloid load and fourfold to sixfold increase in plaque-associated microglia, as well as evidence of greater microglial activation at the site of inflammation. We also found evidence of increased p38 mitogen-activated protein kinase and glycogen synthase kinase-3beta activity, which are believed to contribute to tau phosphorylation. Thus, neuroinflammation regulates amyloid and tau pathology in opposing ways, suggesting that it provides a link between amyloid accumulation and changes in tau and raising concerns about the use of immunomodulatory therapies in AD. |
