Plasma Glial Fibrillary Acidic Protein Correlates With Brain Metal Burden in Wilson's Disease

Objective Neuroinflammation driven by extracellular copper contributes to neuronal damage in Wilson's disease (WD). This study investigated the relationship between brain metal burden and peripheral neuroinflammation markers in WD. Methods We conducted a cross‐sectional study involving 89 participants, including patients with WD ( n = 63), asymptomatic ATP7B heterozygous carriers ( n = 12), and age/sex‐matched controls ( n = 14). Brain metal burden was assessed using quantitative susceptibility mapping (QSM) MRI. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels were measured. Clinical severity was evaluated using the mini–Unified Wilson's Disease Rating Scale (UWDRS) and Montreal Cognitive Assessment (MoCA). The influence of copper chelation treatment on biomarker correlations was also examined. Results Patients with WD had a significantly higher level of GFAP ( p = 0.02) and brain metal burden ( p < 0.01) than the control group. Plasma NfL levels were marginally elevated in the WD group ( p = 0.07). Notably, elevated plasma GFAP levels were significantly associated with higher UWDRS scores ( r = 0.35, p < 0.01) and lower MoCA scores ( r = −0.36, p < 0.01). The NfL levels were also correlated with UWDRS ( r = 0.58, p < 0.01) and marginally correlated with MoCA ( r = −0.32, p = 0.02). The brain magnetic susceptibility value was positively correlated with increased plasma GFAP level, particularly in the putamen ( p < 0.001), which was more prominent in WD patients without chelating agent treatment ( r = 0.58, p < 0.001). Interpretations Plasma GFAP levels reflect both clinical severity and brain metal accumulation in WD, with this association influenced by copper chelation therapy.