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‘Neuroinflammation’ differs categorically from inflammation: transcriptomes of Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases compared

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Abstract

‘Neuroinflammation’ has become a widely applied term in the basic and clinical neurosciences but there is no generally accepted neuropathological tissue correlate. Inflammation, which is characterized by the presence of perivascular infiltrates of cells of the adaptive immune system, is indeed seen in the central nervous system (CNS) under certain conditions. Authors who refer to microglial activation as neuroinflammation confuse this issue because autoimmune neuroinflammation serves as a synonym for multiple sclerosis, the prototypical inflammatory disease of the CNS. We have asked the question whether a data-driven, unbiased in silico approach may help to clarify the nomenclatorial confusion. Specifically, we have examined whether unsupervised analysis of microarray data obtained from human cerebral cortex of Alzheimer's, Parkinson's and schizophrenia patients would reveal a degree of relatedness between these diseases and recognized inflammatory conditions including multiple sclerosis. Our results using two different data analysis methods provide strong evidence against this hypothesis demonstrating that very different sets of genes are involved. Consequently, the designations inflammation and neuroinflammation are not interchangeable. They represent different categories not only at the histophenotypic but also at the transcriptomic level. Therefore, non-autoimmune neuroinflammation remains a term in need of definition.

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Abbreviations

AD:

Alzheimer’s disease

CNS:

Central nervous system

DM:

Dermatomyositis

EAE:

Experimental autoimmune encephalomyelitis

IBD:

Inflammatory bowel disease

JDM:

Juvenile dermatomyositis

MHC:

Major histocompatibility complex

MS:

Multiple sclerosis

PD:

Parkinson’s disease

SCZ:

Schizophrenia

UC:

Ulcerative colitis

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Acknowledgements

M.D.F. is supported by a grant from the Deutsche Forschungsgemeinschaft. P.M. is funded by the ARC Future Fellowship FT120100060. This work was partially funded by the Maitland Cancer Appeal Committee, NSW, Australia and the Australian Research Council (ARC) Discovery Project Grants DP120102576 and DP140104183. We would like to thank Natalie de Vries for comments on the final version of this manuscript.

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  1. Max Planck Institute of Psychiatry, Kraepelinstraße 2, 80804, Munich, Germany

    Michaela D. Filiou

  2. Centre for Bioinformatics, Biomarker Discovery and Information-based Medicine, Hunter Medical Research Institute, University of Newcastle, Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia

    Ahmed Shamsul Arefin & Pablo Moscato

  3. Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, University of Sydney, 94 Mallett Street, Camperdown, Sydney, NSW 2050, Australia

    Manuel B. Graeber

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  1. Michaela D. Filiou
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  2. Ahmed Shamsul Arefin
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Correspondence to Manuel B. Graeber.

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Filiou, M.D., Arefin, A.S., Moscato, P. et al. ‘Neuroinflammation’ differs categorically from inflammation: transcriptomes of Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases compared. Neurogenetics 15, 201–212 (2014). https://doi.org/10.1007/s10048-014-0409-x

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