A beneficial role for IL-1β in Alzheimer disease?
Cynthia A. Lemere
Cynthia A. Lemere
Published June 1, 2007
Citation Information: J Clin Invest. 2007;117(6):1483-1485. https://doi.org/10.1172/JCI32356.
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Commentary

A beneficial role for IL-1β in Alzheimer disease?

Abstract

While the term neuroinflammation often conjures up images of cellular damage, mounting evidence suggests that certain proinflammatory molecules, such as the cytokine IL-1β, may have beneficial and protective effects. In a report in this issue of the JCI, Shaftel and coworkers have generated an elegant mouse model in which local hippocampal overexpression of IL-1β in an Alzheimer disease (AD) transgenic mouse model resulted not in the expected exacerbation of the amyloid β plaque deposition common to AD, but instead in plaque amelioration (see the related article beginning on page 1595). Thus, manipulation of the immune system may be a potential therapeutic approach to protect against AD, although further studies are needed to understand all of the downstream effects of this manipulation.

Authors

Cynthia A. Lemere

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Figure 1

Overexpression of IL-1β activates glial cells and reduces Aβ plaque deposition in a mouse model of AD.

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Overexpression of IL-1β activates glial cells and reduces Aβ plaque depo...
In this issue of the JCI, Shaftel and colleagues (5) used XAT technology to generate IL-1βXAT transgenic mice and crossbred these mice with APP/PS1 mice, a mouse model used to study AD. Intrahippocampal injection of FIV-Cre at 6 months of age locally activated the IL-1β transgene and increased the levels of IL-1β and glial fibrillary acid protein (GFAP), indicative of astrocytic activation, as well as Iba-1 and MHC class II, indicative of microglial activation. One month later, instead of observing a worsening of AD-like pathogenesis as expected, the authors found that IL-1β overexpression in the APP/PS1+IL-1β mouse resulted in reduced Aβ plaque deposition and lower insoluble Aβ levels in the injected ipsilateral hippocampus compared with the control-injected contralateral hippocampus. Levels of APP and β-secretase, one of the APP-cleaving enzymes responsible for generating Aβ, were unchanged, suggesting that Aβ production was not affected. Instead, IL-1β overexpression led to increased microglial activation and possibly, as the authors hypothesize, clearance of Aβ deposits by microglial phagocytosis. CA, cornu ammonis; DG, dentate gyrus.