Abstract
OBJECTIVE: To elucidate the association between serum neurofilament light chain (NfL) levels and structural brain alterations in individuals exhibiting white matter hyperintensities (WMHs), as well as to investigate the potential utility of serum NfL as a predictive biomarker for the progression of WMH. METHODS: A total of 151 subjects were included in the study, among whom 117 demonstrated the presence of white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). We assessed the relationship between changes in serum neurofilament light chain (NfL) levels and alterations in brain volume across three distinct groups. Additionally, we analyzed trends in brain structural changes and serum NfL level variations within the population exhibiting varying severities of WMHs, exploring the correlation between these two variables. RESULTS: Serum NfL levels were significantly elevated in individuals with WMHs compared to those with none-low WMHs (p < 0.001). Furthermore, higher serum NfL levels were observed in individuals with severe-moderate WMHs compared to those with mild WMHs (p < 0.01). Within the mild WMHs group, serum NfL levels exhibited a negative correlation with gray matter volume. In contrast, within the severe to moderate WMHs group, serum NfL levels were negatively correlated with both gray matter volume (GMV) and white matter volume (WMV). Voxel-based morphometry (VBM) analysis indicated the presence of gray matter atrophy in several brain regions when comparing the none-low WMHs group with the severe to moderate WMHs group, as well as when comparing the mild WMHs group with the severe-moderate WMHs group. However, no significant differences were observed in the comparison between the none to low WMHs group and the mild WMHs group. CONCLUSION: Serum NfL levels have been observed to rise in conjunction with the increasing severity of WMH and show a correlation with gray matter atrophy in individuals exhibiting WMHs. These levels are anticipated to serve as a biological marker for predicting the progression of WMH.