Tardbp ala382thr mutation in multiple sclerosis: A possible role in brain atrophy

Background: Multiple Sclerosis (MS) is a chronic multifactorial disease of the central nervous system, specifically characterized by inflammatory demyelination and primary neurode-generation. Recently, a possible role for the TARDBP Ala382Thr mutation in inducing neurode-generation in MS has been hypothesized, considering its confirmed role in other neurodegenerative diseases. The aim of the present study was to explore if this mutation plays a role in inducing or enhancing the brain atrophy in MS. Methods: The study included a group of MS patients carrying the TARDBP Ala382Thr mutation, genetically tested at the MS Centre of the University of Cagliari. Mutated MS patients were age, sex, disease course and EDSS-matched with MS patients without mutation, randomly selected from the genetic database. Recruited patients underwent a brain MRI with a 1.5 Tesla Siemens scanner. Volumes of Whole Brain (WB), White Matter (WM) and Grey Matter (GM) were estimated with SIENAX. The difference in brain volumes was assessed with independent samples t-test. Results: Lower WM volumes resulted significantly associated to mutated group (688.68 ml +/- 36.55 vs. 713,22 ml +/- 27.34; p 0.03). No difference in WB and GM volumes was reported between the two groups. Discussion and Conclusion: Despite this mutation does not play a major role in MS pathogenesis, it may contribute in enhancing the brain atrophy, especially for WM. However, additional studies in other MS populations are needed to better know this issue.