Neural damage and inflammation in myotonic dystrophy type 1: Longitudinal analysis of serum NFL, GFAP, and IL-6

Abstract

Introduction: Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disease affecting the central nervous system (CNS). Blood-based biomarkers such as neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and interleukin-6 (IL-6) offer potential as non-invasive indicators of CNS dysfunction and/or inflammation. However, their longitudinal dynamics and clinical relevance in DM1 remain unclear. Additionally, sex-related differences in these biomarkers are poorly understood. This study aimed to investigate NFL, GFAP, and IL-6 serum levels in patients with DM1, examine sex-differences, track changes over four years, and explore associations with genetic, muscular, cognitive, and neuroimaging outcomes.

Method: Retrospective data from 70 DM1 patients and 54 healthy controls (HC) were analyzed. Longitudinal data were available for 68 participants (39 DM1, 29 HC). Biomarkers were measured using the ELLA immunoassay. DM1 patients had data on genetic, muscular, cognitive and structural brain outcomes. Analyses were adjusted for age.

Results: NFL and IL-6 levels were significantly higher in DM1 patients compared to HC, while GFAP levels did not differ. Male DM1 patients exhibited higher NFL and IL-6 levels compared to females. No significant longitudinal changes were observed over a four-year period. NFL and IL-6 levels correlated with larger genetic expansions and poorer cognitive performance.

Discussion: NFL and IL-6 may reflect neural damage and systemic inflammation in DM1 and could serve as biomarkers of cognitive dysfunction. However, their limited longitudinal sensitivity suggests longer follow-up is needed to evaluate their utility for disease monitoring.

Keywords: Blood-based biomarkers; Brain; CNS; Cognition; DM1; Follow-up; Steinert’s disease.