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.
Highlights
In the central nervous system, neurofilaments are cytoskeletal components of neurons that are abundant in axons, where neurofilaments provide structural support and contribute maintaining size, shape, and caliber of the axons [1]
In the present study we focus especially on a subset of tracts of interest, that consistently have been reported as affected in behavioral variant FTD (bvFTD) in previous diffusion tensor imaging (DTI) studies [20,21,23] namely: the fronto-occipital fasciculus (FOF), the superior longitudinal fasciculus (SLF), the uncinate fasciculus (UF), cortico-spinal tract (CST), the dorsal cingulum bundle, the anterior thalamic radiation (ATR), and the inferior/ hippocampal portion of the cingulum bundle
This study explored for the first time the association between plasma neurofilament light chain (NfL) levels and DTI metrics in a group of patients affected by bvFTD
Summary
In the central nervous system, neurofilaments are cytoskeletal components of neurons that are abundant in axons, where neurofilaments provide structural support and contribute maintaining size, shape, and caliber of the axons [1]. Neurofilament light chain (NfL) is the most abundant and soluble of the neurofilament subunits and can be reliably measured in cerebrospinal fluid (CSF) as well as in blood. NfL has rapidly emerged as one of the most promising fluid biomarkers in several neurodegenerative conditions including Alzheimer’s disease [4] and atypical parkinsonian disorders [5]. On a markedly increased CSF levels of NfL in frontotemporal dementia (FTD) as compared with controls and Alzheimers disease was found [6], a finding valid for NfL in blood [7], and increased peripheral NfL has been reliably validated in FTD [8,9,10,11,12,13]. A dramatic increase compared with controls and other neurodegenerative conditions has been exhaustively documented in amyotrophic lateral sclerosis (ALS) [14,15,16]
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