White JA, Manelli AM, Holmberg KH, et al. Differential effects of oligomeric and fibrillar amyloid-beta 1-42 on astrocyte-mediated inflammation

Department of Cell and Molecular Biology, Northwestern University, Evanston, Illinois, United States
Neurobiology of Disease (Impact Factor: 5.08). 05/2005; 18(3):459-65. DOI: 10.1016/j.nbd.2004.12.013
Source: PubMed


Activated glia, as a result of chronic inflammation, are associated with amyloid-beta peptide (Abeta) deposits in the brain of Alzheimer's disease (AD) patients. In vitro, glia are activated by Abeta inducing secretion of pro-inflammatory molecules. Recent studies have focused on soluble oligomers (or protofibrils) of Abeta as the toxic species in AD. In the present study, using rat astrocyte cultures, oligomeric Abeta induced initial high levels of IL-1beta decreasing over time and, in contrast, fibrillar Abeta increased IL-1beta levels over time. In addition, oligomeric Abeta, but not fibrillar Abeta, induced high levels of iNOS, NO, and TNF-alpha. Our results suggest that oligomers induced a profound, early inflammatory response, whereas fibrillar Abeta showed less increase of pro-inflammatory molecules, consistent with a more chronic form of inflammation.

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Available from: Kristina H Holmberg
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    • "Mixed glial cultures (95% astrocytes, 5% microglia) were isolated from APOE-TR and APOE-KO mice as described (White et al. 2005; Nwabuisi-Heath et al. 2012). Glial cultures (24-well plates) were incubated with oAb42 (0– 10 lM) (see Stine et al. 2003; White et al. 2005 for details) or LPS (0-100 ng/mL), +/À LPSRS, IAXO101, IAXO103, IAXO202 (Innaxon, Tewkesbury, UK), MW181 (Watterson et al. 2013, Bachstetter et al. 2014), or vehicle control, at the concentrations indicated in the figures (N.B. "
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