Plasma Glial Fibrillary Acidic Protein Correlates With Brain Metal Burden in Wilson's Disease.
Journal
Annals of clinical and translational neurology
Journal Volume
12
Journal Issue
12
ISSN
2328-9503
Date Issued
2025-12
Author(s)
Fan, Sung-Pin
Chen, Ya-Fang
Li, Cheng-Hsuan
Kuo, Yih-Chih
Hwu, Wuh-Liang
Tseng, Tai-Chung
Su, Tung-Hung
Hsu, Chien-Ting
Lin, Chin-Hsien
Ni, Yen-Hsuan
Abstract
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.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.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).Plasma GFAP levels reflect both clinical severity and brain metal accumulation in WD, with this association influenced by copper chelation therapy.
Subjects
Wilson's disease
brain MRI
chelating agents
glial fibrillary acidic protein
neuroinflammation
quantitative susceptibility mapping
SDGs
Type
journal article