Multiple sclerosis (MS) is a neurological disease causing myelin and axon damage through inflammatory and autoimmune processes. Despite affecting millions worldwide, understanding its genetic pathways remains limited. The choroid plexus (ChP) has been studied in neurodegenerative processes and diseases like MS due to its dysregulation, yet its role in MS pathophysiology remains unclear. Our work re-evaluates the ChP transcriptome in progressive MS patients and compares gene expression profiles using diverse methodological strategies. Samples from patient and healthy control RNASeq sequencing of brain tissue from post-mortem patients (GEO: GSE137619) were used. After an evaluation and quality control of these data, they had their transcripts mapped and quantified against the reference transcriptome GRCh38/hg38 of Homo sapiens using three strategies to identify differentially expressed genes in progressive MS patients. Functional analysis of genes revealed their involvement in immune processes, cell adhesion and migration, hormonal actions, amino acid transport, chemokines, metals, and signaling pathways. Our findings can offer valuable insights for progressive MS therapies, suggesting specific genes influence immune cell recruitment and potential ChP microenvironment changes. Combining complementary approaches maximizes literature coverage, facilitating a deeper understanding of the biological context in progressive MS.