Utility of serum neurofilament light chain and glial fibrillary acidic protein as diagnostic biomarkers of freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is one of the most distressing features of Parkinson’s disease (PD), increasing the risks of fractures and seriously affecting patients’ quality of life. We aimed to examine the potential diagnostic roles of serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in PD patients with FOG (PD-FOG). We included 99 patients, comprising 54 PD patients without FOG (PD-NoFOG), 45 PD-FOG and 37 healthy controls (HCs). Our results indicated serum markers were significantly higher in PD-FOG and postural instability and gait difficulty (PIGD) motor subtype patients than in PD-NoFOG and non-PIGD subtype patients ( P  < 0.05), respectively. Patients with high concentrations of the markers NFL and GFAP had higher PIGD scores and greater FOG severity than those with low concentrations. Moreover, serum levels of both NFL and GFAP were significantly positively associated with age, FOG severity, PD-FOG status, and negatively associated with Mini-Mental State Examination (MMSE) scores. Logistic regression analysis identified serum levels of NFL and GFAP as independent risk factors for PD-FOG. Mediation analysis revealed that MMSE scores fully mediated the relationship between serum GFAP levels and FOG-Q scores, accounting for 33.33% of the total effects (indirect effect = 0.01, 95% CI 0.01–0.02). NFL levels differentiated PD-FOG from PD-NoFOG with reliable diagnostic accuracy (AUC 0.75, 95% CI 0.66–0.84), and the combination of NFL, GFAP, duration and MMSE scores demonstrated high accuracy (AUC 0.84, 95% CI 0.76–0.91). Our findings support the notion that NFL and GFAP may be potential biomarkers for the diagnosis of PD-FOG.