Comparative Analysis of Mouse CSF Proteins in Experimental Autoimmune Encephalomyelitis Model and Cuprizone-Induced Demyelination Model by Olink Proteomics

Multiple sclerosis (MS) is marked by an autoimmune-driven inflammatory response within the central nervous system (CNS), resulting in demyelination and associated neurological impairment. To investigate the pathways involved in MS-related neuroinflammation, we performed cerebrospinal fluid (CSF) proteomic profiling (Olink®) across two murine models, i.e., the experimental autoimmune encephalomyelitis (EAE) and the cuprizone (CPZ)-induced demyelination models. Out of the 92 proteins analyzed, five (CCL2, CCL3, EDA2R, Fas, and HGF) were consistently dysregulated in both models, highlighting shared neuroinflammatory features alongside distinct pathological processes. In the EAE model, 31 proteins were upregulated compared to CPZ-intoxicated mice and controls and were mainly related to T cell development, effector functions and migration, reflecting the model’s lymphocyte-centric nature. In contrast, the CPZ model showed a downregulation of a single protein, SEZ6L2, when compared to both EAE and controls. These findings emphasize the divergent protein profiles of CSF in EAE and CPZ models and underscore the different inflammatory pathways engaged in distinct pathophysiological mechanisms of MS.