Differential effects of oligomeric and fibrillar amyloid-beta 1-42 on astrocyte-mediated inflammation.
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.
White
Jill A
JA
Department of Medicine, Division of Geriatrics, Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA.
Manelli
Arlene M
AM
Holmberg
Kristina H
KH
Van Eldik
Linda J
LJ
Ladu
Mary Jo
MJ
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)