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Type-I interferon pathway in neuroinflammation and neurodegeneration: focus on Alzheimer’s disease

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
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Abstract

Past research in Alzheimer’s disease (AD) has largely been driven by the amyloid hypothesis; the accompanying neuroinflammation seen in AD has been assumed to be consequential and not disease modifying or causative. However, recent data from both clinical and preclinical studies have established that the immune-driven neuroinflammation contributes to AD pathology. Key evidence for the involvement of neuroinflammation in AD includes enhanced microglial and astroglial activation in the brains of AD patients, increased pro-inflammatory cytokine burden in AD brains, and epidemiological evidence that chronic non-steroidal anti-inflammatory drug use prior to disease onset leads to a lower incidence of AD. Identifying critical mediators controlling this neuroinflammation will prove beneficial in developing anti-inflammatory therapies for the treatment of AD. The type-I interferons (IFNs) are pleiotropic cytokines that control pro-inflammatory cytokine secretion and are master regulators of the innate immune response that impact on disorders of the central nervous system. This review provides evidence that the type-I IFNs play a critical role in the exacerbation of neuroinflammation and actively contribute to the progression of AD.

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Acknowledgements

This study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia.

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Authors and Affiliations

  1. Neuropharmacology Laboratory, Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC, Australia

    Juliet M. Taylor, Zachery Moore & Peter J. Crack

  2. Department of Neurobiology, The University of Chicago, Chicago, IL, 60637, USA

    Myles R. Minter

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  1. Juliet M. Taylor
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  2. Zachery Moore
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  3. Myles R. Minter
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  4. Peter J. Crack
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JMT, ZM, MRM, and PJC all contributed to the writing of this manuscript.

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Correspondence to Peter J. Crack.

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Taylor, J.M., Moore, Z., Minter, M.R. et al. Type-I interferon pathway in neuroinflammation and neurodegeneration: focus on Alzheimer’s disease. J Neural Transm 125, 797–807 (2018). https://doi.org/10.1007/s00702-017-1745-4

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