Distinct gene expression profiles in leukocortical demyelinated white and grey matter areas of Multiple Sclerosis patients

ABSTRACT Demyelination of the CNS is a prominent pathological hallmark of Multiple Sclerosis (MS) and affects both white (WM) and grey matter (GM). However, demyelinated WM and GM areas exhibit clear pathological differences, most notably the presence or absence of inflammation and activated glial cells in WM and GM, respectively. In order to gain more insight into the differential pathology of demyelinated WM and GM areas, we micro-dissected neighbouring WM and GM demyelinated areas as well as normal appearing matter from leukocortical lesions of human post-mortem material and used these samples for RNA-sequencing. Our data show that even neighbouring WM and GM demyelinated areas share only 10% overlap in gene expression, implying a distinct gene expression profile, which is extending to a specific glial cell related signature. We propose that, based on their distinct expression profile, pathological processes in neighbouring WM and GM are likely different which could have implications for the efficacy of current MS treatments.