Solomon S. Shaftel, Stephanos Kyrkanides, John A. Olschowka, Jen-nie H. Miller, Renee E. Johnson, M. Kerry O’Banion
J Clin Invest.
2007;
117(6):1595–1604
doi:10.1172/JCI31450
This article Copyright © 2007, The American Society for Clinical Investigation
Abstract
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euroinflammation is a conspicuous feature of Alzheimer disease (AD) pathology and is thought to contribute to the ultimate neurodegeneration that ensues. IL-1β has emerged as a prime candidate underlying this response. Here we describe a transgenic mouse model of sustained IL-1β overexpression that was capable of driving robust neuroinflammation lasting months after transgene activation. This response was characterized by astrocytic and microglial activation in addition to induction of proinflammatory cytokines. Surprisingly, when triggered in the hippocampus of the APPswe/PS1dE9 mouse model of AD, 4 weeks of IL-1β overexpression led to a reduction in amyloid pathology. Congophilic plaque area fraction and frequency as well as insoluble amyloid beta 40 (Aβ40) and Aβ42 decreased significantly. These results demonstrate a possible adaptive role for IL-1β–driven neuroinflammation in AD and may help explain recent failures of antiinflammatory therapeutics for this disease.
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