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Assessing the contribution of inflammation in models of Alzheimer's disease.
MedLine Citation:
PMID:  21787318     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Inflammation has long been proposed as having a role in AD (Alzheimer's disease), although it remains unclear whether inflammation represents a cause or consequence of AD. Evidence from the clinical setting in support of a role for inflammation in AD includes increased expression of inflammatory mediators and microglial activation in the post-mortem AD brain. Also, epidemiological studies on AD patients under long-term treatment with non-steroidal anti-inflammatory drugs suggest some benefits, although recent prospective trials showed no effect. Furthermore, in AD patients, infection and other systemic inflammatory events worsen symptoms. Finally, several inflammatory genes are associated with increased risk of AD. Therefore, to elucidate the underlying mechanisms of AD and the role of inflammation, researchers have turned to experimental models and here we present a short overview of some key findings from these studies. Activation of microglia is seen in various transgenic models of AD, with both a protective role and a detrimental role being ascribed to it. Early microglial activation is probably beneficial in AD, through phagocytosis of amyloid β-peptide. At later stages however, pro-inflammatory cytokine release from microglia could contribute to neuronal demise. A better understanding of microglial phenotype at the various stages of AD is therefore still required. Although most studies suggest a detrimental role for pro-inflammatory cytokines such as interleukin-1 and tumour necrosis factor in AD, contradictory findings do exist. Age-related and differential cellular expression of these inflammatory mediators is probably a key determinant of their exact contribution to AD. In conclusion, there is no doubt that inflammatory processes are part of the pathophysiology of AD, but a better understanding of the exact contribution at different stages of the disease process is still required before appropriate treatment strategies can be devised.
Authors:
Hannah Johnston; Herve Boutin; Stuart M Allan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical Society transactions     Volume:  39     ISSN:  1470-8752     ISO Abbreviation:  Biochem. Soc. Trans.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506897     Medline TA:  Biochem Soc Trans     Country:  England    
Other Details:
Languages:  eng     Pagination:  886-90     Citation Subset:  IM    
Affiliation:
Faculty of Life Sciences, University of Manchester, AV Hill Building, Manchester M13 9PT, U.K.
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