Plasma neurofilament light levels correlate with white matter damage prior to Alzheimer's disease: results from ADNI

Background The blood biomarker neurofilament light (NFL) is one of the most widely used for monitoring Alzheimer's disease (AD). According to recent research, a higher NFL plasma level has a substantial predictive value for cognitive deterioration in AD patients. Diffusion tensor imaging (DTI) is an MRI-based approach for detecting neurodegeneration, white matter (WM) disruption, and synaptic damage. There have been few studies on the relationship between plasma NFL and WM microstructure integrity. Aims The goal of the current study is to assess the associations between plasma levels of NFL, CSF total tau, phosphorylated tau181 (P-tau181), and amyloid-beta (A beta) with WM microstructural alterations. Methods We herein have investigated the cross-sectional association between plasma levels of NFL and WM microstructural alterations as evaluated by DTI in 92 patients with mild cognitive impairment (MCI) provided by Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. We analyzed the potential association between plasma NFL levels and radial diffusivity (RD), axial diffusivity (AxD), mean diffusivity (MD), and fractional anisotropy (FA) in each region of the Montreal Neurological Institute and Hospital (MNI) atlas, using simple linear regression models stratified by age, sex, and APOE epsilon 4 genotype. Results Our findings demonstrated a significant association between plasma NFL levels and disrupted WM microstructure across the brain. In distinct areas, plasma NFL has a negative association with FA in the fornix, fronto-occipital fasciculus, corpus callosum, uncinate fasciculus, internal capsule, and corona radiata and a positive association with RD, AxD, and MD values in sagittal stratum, corpus callosum, fronto-occipital fasciculus, corona radiata, internal capsule, thalamic radiation, hippocampal cingulum, fornix, and cingulum. Lower FA and higher RD, AxD, and MD values are related to demyelination and degeneration in WM. Conclusion Our findings revealed that the level of NFL in the blood is linked to WM alterations in MCI patients. Plasma NFL has the potential to be a biomarker for microstructural alterations. However, further longitudinal studies are necessary to validate the predictive role of plasma NFL in cognitive decline.