Distinct gene expression in demyelinated white and grey matter areas of patients with multiple sclerosis

Thecla A. van Wageningen, Emma Gerrits, Nieske Brouwer, John J. P. Breve, Jeroen J. G. Geurts, Bart J. L. Eggen, H. W. G. M. (Erik) Boddeke, Anne-Marie van Dam

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Demyelination of the central nervous system is a prominent pathological hallmark of multiple sclerosis and affects both white and grey matter. However, demyelinated white and grey matter exhibit clear pathological differences, most notably the presence or absence of inflammation and activated glial cells in white and grey matter, respectively. In order to gain more insight into the differential pathology of demyelinated white and grey matter areas, we micro-dissected neighbouring white and grey matter demyelinated areas as well as normal-appearing matter from leucocortical lesions of human post-mortem material and used these samples for RNA sequencing. Our data show that even neighbouring demyelinated white and grey matter of the same leucocortical have a distinct gene expression profile and cellular composition. We propose that, based on their distinct expression profile, pathological processes in neighbouring white and grey matter are likely different which could have implications for the efficacy of treating grey matter lesions with current anti-inflammatory-based multiple sclerosis drugs.

Original languageEnglish
Article numberfcac005
JournalBrain Communications
Issue number2
Publication statusPublished - 1 Mar 2022


  • Glial cells
  • Grey matter demyelination
  • Leucocortical lesions
  • Multiple sclerosis
  • RNA sequencing

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