Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

Abstract

Neurofilaments are the major structural proteins of the neuronal cytoskeleton and are classified according to molecular weight into heavy, intermediate, and light chains. They are released into the interstitial fluid and cerebrospinal fluid (CSF) as a consequence of axonal damage. In particular, the light chain (NfL) represents the most abundant and soluble subunit and has been demonstrated to be increased in the CSF of patients with inflammatory, degenerative, vascular, or traumatic injuries in correlation with clinical and radiological activity. Similar results have been obtained measuring serum NfL with high-sensitivity single-molecule array, which enables reliable and repeatable measurement of the low NfL concentrations in serum. In particular, CSF and serum NfL values are strongly correlated in patients with multiple sclerosis (MS) and have been demonstrated to be increased in patients with MS and clinically isolated syndromes (CIS) in accordance with clinical and radiological activity. NfL levels increase in patients with a recent relapse and seem to predict cognitive impairment, longterm outcome, and conversion of CIS to MS. The few available data on patients with other demyelinating diseases suggest that NfL levels are also increased in neuromyelitis optica spectrum disorders and related conditions in correlation with attack severity, suggesting that axonal damage may occur in these disorders. We herein report and discuss published data on the role of NfL as a possible predictor of disease activity, clinical outcome and treatment response in patients with demyelinating conditions of the central nervous system.

Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum

“…Decreased Non‐Gaussianity (NG) from MAP‐MRI suggests reduced tissue complexity and is likely a sensitive marker of axonal loss and demyelination, 15 which are 2 hallmark features of AD‐related WM degeneration 43,44 . NfL, which was predictive of NG, NG ⊥ , and NG ∥ in our sample, is sensitive to both 45,46 . Moreover, NG ⊥ had a strikingly widespread association with α‐synuclein, a presynaptic protein and known marker for synaptic degeneration 22 .…”

“… 43 , 44 NfL, which was predictive of NG, NG ⊥ , and NG ∥ in our sample, is sensitive to both. 45 , 46 Moreover, NG ⊥ had a strikingly widespread association with α‐synuclein, a presynaptic protein and known marker for synaptic degeneration. 22 In this context, it is likely that damaged synapses (in the cortices) are concurrently affecting nearby (subcortical) WM and that NG ⊥ , by detecting subtle increases in diffusion Gaussianity in the affected area, is sensitive to this damage.…”

Neurofilament light protein as a biomarker in depression and cognitive function

“…NfL is an emerging biomarker of neural health or injury [9]. Neurofilaments are vital constituents of the neuronal cytoskeleton and are particularly abundant in the axons of neurons [10]. Neurofilaments form the assembly and stability of the cytoskeleton through cross-bridging and interconnecting with other components of the cytoskeleton [11 ▪ ].…”

Serum neurofilament light chain and cognition decline in US elderly: A cross‐sectional study

“…Although the biological mechanisms underlying the relationship between elevated sNfL levels and cognitive decline are not yet fully understood, we can speculate that the following reasons may contribute to this association based on existing evidence. First, as a structural protein widely distributed in neuronal axons, Neurofilaments are primarily involved in maintaining the stability of the cytoskeleton 81,82 . Among the four subunits of Neurofilaments, NfL is the most abundant and soluble, making it the most easily detectable subunit of Neurofilaments 83 .…”

“…First, as a structural protein widely distributed in neuronal axons, Neurofilaments are primarily involved in maintaining the stability of the cytoskeleton. 81 , 82 Among the four subunits of Neurofilaments, NfL is the most abundant and soluble, making it the most easily detectable subunit of Neurofilaments. 83 When axonal damage occurs, NfL is released into the extracellular fluid and can be detected in cerebrospinal fluid or peripheral blood.…”