Differential effects of oligomeric and fibrillar amyloid-β1-42 on astrocyte-mediated inflammation

Activated glia, as a result of chronic inflammation, are associated with amyloid-beta peptide (A beta) deposits in the brain of Alzheimer's disease (AD) patients. In vitro, glia are activated by A beta inducing secretion of pro-inflammatory molecules. Recent studies have focused on soluble oligomers (or protofibrils) of A beta as the toxic species in AD In the present study, using rat astrocyte cultures, oligomeric A beta induced initial high levels of IL-1 beta decreasing over time and, in contrast, fibrillar A beta increased IL-1 beta levels over time. In addition, oligomeric A beta, but not fibrillar A beta, induced high levels of iNOS, NO, and TNF-alpha. Our results suggest that oligomers induced a profound, early inflammatory response, whereas fibrillar A showed less increase of pro-inflammatory molecules, consistent with a more chronic form of inflammation. (c) 2005 Elsevier Inc. All rights reserved.