The role of the choroid plexus in the pathophysiology and progression of multiple sclerosis: a systematic review of preclinical studies in human samples and animal research

Abstract Multiple sclerosis is a chronic neuroinflammatory central nervous system disease characterised by demyelination, neurodegeneration and progressive disability accumulation. Although autoimmune mechanisms are considered central to disease pathogenesis, the precise pathways in which they occur remain incompletely understood. The choroid plexus has emerged as an important mediator in this neuroinflammatory disease. In fact, imaging studies have demonstrated that, in multiple sclerosis brains, there is an enlargement and inflammation of the choroid plexus, which correlates with disease activity and progression. However, the molecular and cellular mechanisms underlying choroid plexus involvement in multiple sclerosis remain poorly characterised and understood, with fragmented evidence across the current literature. This systematic review aims to synthesise the existing experimental and human evidence on the role of the choroid plexus in the pathophysiology and progression of multiple sclerosis. Literature positions the choroid plexus as a crucial player in multiple sclerosis disease, serving not only as a permissive barrier for immune cell entry but also as a dynamic neuroimmune interface that participates in signalling pathways, shaping immune infiltration and neuroinflammation. In this systematic review, we conclude that the choroid plexus plays a multifaceted role in multiple sclerosis pathophysiology and progression through mechanisms that include immune infiltration, barrier disruption and genomic changes. Further investigation to clearly establish temporal and causal relationships between these already investigated mechanisms would be beneficial to better understand multiple sclerosis pathophysiology and motivate research towards novel multiple sclerosis treatment strategies.