Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia

Abstract

Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo , especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.

Plasma neurofilament light and cerebrospinal fluid biomarkers are associated with white matter damage in Alzheimer's disease

“…Plasma NFL has a negative correlation with FA and positive correlation with RD, AD, and MD values in bilateral Cingulum, bilateral hippocampal cingulum, bilateral Anterior corona radiate, Left Anterior limb of internal capsule, Right Posterior thalamic radiation, Right Retrolenticular part of internal capsule, bilateral Superior corona radiate, bilateral Superior fronto-occipital fasciculus, Right Inferior fronto-occipital fasciculus, Left Superior longitudinal fasciculus, Right Sagittal stratum, Bilateral full corpus callosum, and Bilateral fornix. Our ndings are in line with Spotorno et al indicates higher plasma NFL is associated with lower FA value in superior longitudinal fasciculus, the fronto-occipital fasciculus, the anterior thalamic radiation, and the dorsal cingulum bundle in frontotemporal dementia (12). White matter differences between patients with MCI and healthy controls are mostly observed in the corpus callosum, along with limbic pathways, including the fornix, cingulum, and uncinate fasciculus (13).…”

Plasma neurofilament light is associated with white matter damage in Alzheimer's disease

“…Plasma NFL has a negative correlation with FA and a positive correlation with RD, DA, and MD values in the bilateral cingulum, bilateral hippocampal cingulum, bilateral anterior corona radiate, left anterior limb of the internal capsule, right retrolenticular part of the internal capsule, bilateral superior corona radiate, right superior fronto-occipital fasciculus, right inferior fronto-occipital fasciculus, left superior longitudinal fasciculus, right sagittal stratum, bilateral full corpus callosum, and bilateral fornix. Our ndings are in line with Spotorno et al who indicate that higher plasma NFL is associated with lower FA value in superior longitudinal fasciculus, the fronto-occipital fasciculus, the anterior thalamic radiation, and the dorsal cingulum bundle in frontotemporal dementia (18). White matter differences between patients with MCI and healthy controls are mostly observed in the corpus callosum, along with limbic pathways, including the fornix, cingulum, and uncinate fasciculus (19).…”

Blood Biomarkers in Frontotemporal Dementia: Review and Meta-Analysis

“…Other molecules that have been investigated as possible biomarkers include cytokines and chemokines, synaptic markers, and micro-RNA. Proinflammatory interleukins (ILs), such as IL-6 in plasma [ 41 ], IL-8 [ 53 ] or IL-15 in CSF, interferon gamma-induced protein 10 (IP-10) and tumor necrosis factor family cytokines (TNF-α) are some of the cytokines and chemokines that have already been measured in FTD patients [ 53 ]. A great number of studies have focused on micro-RNAs (mRNAs) in FTD, with their results showing a potential use of mRNAs both as a diagnostic tool and as a staging tool of FTD [ 54 ].…”