The choroid plexus in progressive multiple sclerosis presents hypoxia and secretory changes that may be related to neuroprotection

The choroid plexus (CP) is a key regulator of central nervous system (CNS) homeostasis through its secretory, immunological and barrier properties. Accumulating evidence suggests that the CP plays a pivotal role in the pathogenesis of multiple sclerosis (MS), but the underlying mechanisms remain largely elusive. To get a comprehensive view on the role of the CP in MS pathogenesis, we studied transcriptomic alterations of the human CP in progressive MS compared to controls using an RNA sequencing approach. We identified 17 genes with significantly higher expression in progressive MS patients relative to that in controls. Among them is the newly described long non-coding RNA HIF1A-AS3. Next to that, we uncovered disease-affected pathways related to hypoxia, secretion and neuroprotection, while only subtle immunological and no barrier alterations were observed. Three of the differentially expressed genes encode for secreted proteins, namely ADM, PAI-1 (SERPINE1) and STC2. Together, these findings provide novel insights to target the CP during MS and promote the secretion of neuroprotective factors into the CNS of progressive MS patients. Overall design: Post-mortem samples from Whole Choroid Plexus of Primary Progressive Multiple Sclerosis patients and non-neurological controls were sequenced using Illumina Hiseq 3000 and differential expression was assesed using DESeq2