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

Michaela D. Filiou, Ahmed Shamsul Arefin, Pablo Moscato, Manuel B. Graeber

'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.