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A dual role for apolipoprotein E in neuroinflammation

Anti- and pro-inflammatory activity

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Abstract

Chronically activated glia associated with amyloid plaques might contribute to neuronal dysfunction in Alzheimer’s disease (AD) through generation of neuroinflammatory molecules. Apolipoprotein E (apoE), also found associated with amyloid plaques, has been hypothesized to serve an anti-inflammatory role in the CNS through its ability to modulate β-amyloid (Aβ)-induced glial activation. To further characterize the effect of apoE on inflammation, we examined the ability of exogenously added human apoE3 and apoE4 to modulate neuroinflammatory responses of cultured rat glia. Apolipoprotein E3 (apoE3) and apoE4 suppressed oligomeric Aβ-induced production of inducible nitric oxide synthase and cyclo-oxygenase-2, supporting an anti-inflammatory role for apoE. Exogenous apoE also inhibited Aβ-induced production of endogenous apoE. However, exogenous apoE in the absence of Aβ stimulated production of the pro-inflammatory cytokine interleukin-1β in an isoform-dependent manner, with apoE4 inducing a significantly greater response than apoE3. These data support the idea that Aβ stimulation of glial apoE limits neuroinflammation but that overproduction of apoE by activated glia might exacerbate inflammation. In addition, the observation that apoE4 has more robust pro-inflammatory activity than apoE3 provides a mechanistic link between the APOE4 allele and AD, and suggests potential apoE-based therapeutic strategies.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, 60611, Chicago, IL

    Ling Guo & Linda J. Van Eldik

  2. Drug Discovery Program, Northwestern University Feinberg School of Medicine, 60611, Chicago, IL

    Ling Guo, Mary Jo LaDu & Linda J. Van Eldik

  3. Department of Medicine, Evanston Northwestern Healthcare Research Institute, 60201, Evanston, IL

    Mary Jo LaDu

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  1. Ling Guo
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  2. Mary Jo LaDu
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  3. Linda J. Van Eldik
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Correspondence to Linda J. Van Eldik.

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Guo, L., LaDu, M.J. & Van Eldik, L.J. A dual role for apolipoprotein E in neuroinflammation. J Mol Neurosci 23, 205–212 (2004). https://doi.org/10.1385/JMN:23:3:205

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  • DOI: https://doi.org/10.1385/JMN:23:3:205

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