Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with multiple sclerosis

• PPAR-gamma level is elevated in the cerebrospinal fluid of patients with multiple sclerosis.
• PPAR-gamma level in the cerebrospinal fluid strongly correlates with cell count and IgG index.
• PPAR-gamma level in the cerebrospinal fluid shows positive association with clinical severity.

Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcriptional factor involved in the regulation of glucose and lipid metabolism, has gained interest as a potential therapeutic target in multiple sclerosis (MS) due to its potent immunoregulatory properties and the therapeutic efficacy of its ligands in experimental autoimmune encephalitis (EAE). Elevated expression of PPARγ has been observed in the spinal cord of EAE mice and in an in vitro model of antigen-induced demyelination; however, no reports have yet been available on the PPARγ status in the central nervous system of human individuals with MS. Aiming to identify a possible alteration, the present study assessed the levels of PPARγ protein in the cerebrospinal fluid (CSF) of MS patients via ELISA technique. We report a pronounced elevation in the CSF levels of PPARγ in MS patients (n = 35) compared to non-inflammatory controls (n = 22). This elevation was independent of blood-CSF barrier integrity, but correlated with CSF white blood cell count and IgG index, associating the observed elevation with neuroinflammation. Controlling for potential confounders, the CSF levels of PPARγ further displayed a moderate but significant association with clinical severity. Corroborating with prior experimental findings, these results may contribute to our understanding about the role of PPARγ in MS, and may implicate this protein as a potential CSF biomarker of the disease.