Unraveling the inflammation-degeneration tangle in early MS: preliminary insights from ferritin, neurogranin, TREM2, and retinal ganglion cell layer.

Abstract

Background: Multiple sclerosis (MS) involves a complex interplay between immune-mediated inflammation and neurodegeneration. Recent advances in biomarker research have provided new insights into the molecular underpinnings of MS, including ferritin, neurogranin, Triggering Receptor Expressed on Myeloid cells 2 (TREM2), and neurofilaments light chain.

Objectives: This pilot study aims to investigate the levels of these biomarkers in the cerebrospinal fluid (CSF) of MS patients and explore their associations with clinical, cognitive, and optical coherence tomography (OCT) parameters.

Methods: This cross-sectional pilot study included 26 patients with relapsing MS (RMS) and 13 symptomatic controls (SCs). Clinical, cognitive, and OCT assessments were performed, and CSF samples were analyzed for ferritin, neurogranin, TREM2, and neurofilaments.

Results: Neurogranin levels were significantly higher in RMS patients compared to SCs (p = 0.04), and the receiver-operating characteristic (ROC) analysis indicated that neurogranin could be considered a disease biomarker (AUC = 0.733, p = 0.01). Ferritin and neurogranin showed a strong positive correlation (r = 0.690, p < 0.01), and both were inversely correlated with retinal ganglion cell layer (GCL) thickness. TREM2 was positively associated with baseline Expanded Disability Status Scale score.

Conclusion: This pilot study suggests that neurogranin may be a potential biomarker at the time of MS diagnosis, and the interplay between ferritin, neurogranin, and TREM2 highlights the complex relationship between inflammation, oxidative stress, and neuronal damage in MS. The inverse association of ferritin and neurogranin with GCL thickness warrants further investigation into the role of iron metabolism and synaptic damage in the early stages of the disease.