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Chronic IL-1β-Mediated Neuroinflammation Mitigates Amyloid Pathology in a Mouse Model of Alzheimer’s Disease without Inducing Overt Neurodegeneration

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Abstract

Neuroinflammation is a local tissue response to injurious stimuli in the central nervous system (CNS) and is characterized by glial reactivity, induction of cytokines and chemokines, and vascular permeability. The cytokine interleukin (IL)-1β is rapidly induced following CNS insult, and is chronically expressed in neurodegenerative disorders such as Alzheimer’s disease (AD). We recently developed a novel method of sustained IL-1β production in the brain to study the link between IL-1β and AD pathogenesis. Utilizing this model, we have previously demonstrated reduction of plaque size and frequency accompanied by a robust neuroinflammatory response. These observations were limited to a single early time point in the course of AD plaque deposition and did not investigate other neurodegenerative endpoints. To extend these observations to other stages of disease progression and evaluate additional pathologic markers, we investigated the effects of age and duration of IL-1β overexpression in the APPswe/PS-1dE9 AD model on a congenic C57BL/6 background. We now report that IL1β overexpression leads to decreased 6E10 immunopositive plaque pathology regardless of age or duration. We also investigated whether IL-1β overexpression led to neuronal apoptosis or cholinergic axonal degeneration in the context of this AD model. Although we could demonstrate apoptosis of infiltrating inflammatory cells, we found no evidence for IL-1 associated apoptosis of neurons or cholinergic axon degeneration even after 5 months of chronic neuroinflammation. Together, these observations point to a neuroprotective role for IL-1β in AD neuropathogenesis.

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Acknowledgments

We thank J. Miller for packaging of FIV and J. Walter and M. Olschowka for animal colony management, sample preparation and viral injections. This work was supported by National Institute of Health Grants RO1 AG030149 and F31 AG031667 to MKO and SBM, respectively.

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No potential conflicts of interest exist.

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Authors and Affiliations

  1. Department of Neurobiology & Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA

    Sarah B. Matousek, Simantini Ghosh, Solomon S. Shaftel, John A. Olschowka & M. Kerry O’Banion

  2. Department of Orthodontics and Pediatric Dentistry, Stony Brook University Medical Center, Stony Brook, NY, 11794, USA

    Stephanos Kyrkanides

  3. University of Rochester Medical Center, 601 Elmwood Avenue, Box 603, Rochester, NY, 14642, USA

    M. Kerry O’Banion

Authors
  1. Sarah B. Matousek
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  2. Simantini Ghosh
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  5. John A. Olschowka
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  6. M. Kerry O’Banion
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Correspondence to M. Kerry O’Banion.

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Matousek, S.B., Ghosh, S., Shaftel, S.S. et al. Chronic IL-1β-Mediated Neuroinflammation Mitigates Amyloid Pathology in a Mouse Model of Alzheimer’s Disease without Inducing Overt Neurodegeneration. J Neuroimmune Pharmacol 7, 156–164 (2012). https://doi.org/10.1007/s11481-011-9331-2

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  • DOI: https://doi.org/10.1007/s11481-011-9331-2

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