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Inflammation in Alzheimer disease: driving force, bystander or beneficial response?

Nature Medicine volume 12, pages 10051015 (2006) | Download Citation

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Abstract

Alzheimer disease is a progressive dementia with unknown etiology that affects a growing number of the aging population. Increased expression of inflammatory mediators in postmortem brains of people with Alzheimer disease has been reported, and epidemiological studies link the use of anti-inflammatory drugs with reduced risk for the disorder. On the initial basis of this kind of evidence, inflammation has been proposed as a possible cause or driving force of Alzheimer disease. If true, this could have important implications for the development of new treatments. Alternatively, inflammation could simply be a byproduct of the disease process and may not substantially alter its course. Or components of the inflammatory response might even be beneficial and slow the disease. To address these possibilities, we need to determine whether inflammation in Alzheimer disease is an early event, whether it is genetically linked with the disease and whether manipulation of inflammatory pathways changes the course of the pathology. Although there is still little evidence that inflammation triggers or promotes Alzheimer disease, increasing evidence from mouse models suggests that certain inflammatory mediators are potent drivers of the disease. Related factors, on the other hand, elicit beneficial responses and can reduce disease.

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Acknowledgements

I would like to thank M. Buckwalter and M. Britschgi for comments on the manuscript, L. Bertram for advice on the use of the AlzGene genetic resource, and O. Arancio and M. Staufenbiel for communicating unpublished data. This work was supported by the John Douglas French Alzheimer's Foundation and the Veterans Administration Geriatric Research, Education and Clinical Center.

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  1. Geriatric Research, Education and Clinical Center, Veterans Administration Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USA and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Mail Code 5235, Stanford, California 94305, USA. twc@stanford.edu

    • Tony Wyss-Coray

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