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

van Wageningen et al. present gene expression data of demyelinated and normal-appearing white and grey matter of multiple sclerosis leucocortical lesions. They find that grey matter lesions primarily feature gene expression indicative of a microglial response while white matter lesions feature astrocytic activation and dystrophic neurons. 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.