Abstract
BackgroundCerebrospinal fluid (CSF) neurofilament light (NfL) is a reliable marker of neuro-axonal damage in different neurological disorders that is related to disease severity. To date, all recent studies performed in human CSF have used the same enzyme-linked immunosorbent assay (ELISA). To confirm the large body of evidence for NfL, we developed a new ELISA method and here we present the performance characteristics of this new ELISA for CSF NfL in different neurological disorders.MethodsWe produced two monoclonal antibodies (NfL21 and NfL23) directed against the NfL core domain, and developed a novel sandwich ELISA method that we evaluated in patients with: 1) inflammatory demyelinating diseases (IDD; n = 97), including multiple sclerosis (MS; n = 59), clinically isolated syndrome (CIS; n = 32), and radiologically isolated syndrome (RIS; n = 6); 2) Alzheimer’s disease (AD; n = 72), including mild cognitive impairment due to AD (MCI-AD, n = 36) and probable AD dementia (AD-dem; n = 36); 3) Parkinson’s disease (PD; n = 30); and 4) other neurological noninflammatory and non-neurodegenerative diseases (OND; n = 30).ResultsOur new NfL ELISA showed a good analytical performance (inter-plate coefficient of variation (CV) < 13%), with no cross-reactivity with neurofilament medium and heavy (NfM and NfH). With respect to the other available ELISAs, CSF NfL showed the same range of values with a strong correlation (r = 0.9984, p < 0.001) between the two methods. CSF NfL levels were significantly higher in MCI-AD/AD-dem and IDD patients as compared with both PD and OND patients. The highest discriminative power was obtained between IDD and OND patients (area under the curve (AUC) 0.87, 95% confidence interval (CI) 0.80–0.95). Within the IDD group, CSF NfL positively correlated with several clinical and radiological disease severity parameters.ConclusionsThese results show a good analytical performance of the new ELISA for quantification of NfL concentrations in the CSF. CSF NfL is confirmed to be a reliable marker in AD and MS, and a disease-severity marker in MS patients.
Highlights
Cerebrospinal fluid (CSF) neurofilament light (NfL) is a reliable marker of neuro-axonal damage in different neurological disorders that is related to disease severity
Increased CSF NfL concentrations have been reported in multiple sclerosis (MS) [6], subcortical vascular dementia [7], Alzheimer’s disease (AD) [5], frontotemporal dementia (FTD) [8], Creutzfeldt-Jakob disease (CJD) [9], atypical parkinsonisms [10], normal pressure hydrocephalus [11], amyotrophic lateral sclerosis (ALS) [12], central nervous system (CNS) infections [13], and brain traumatic injury [14]
The residuals for the curve fitting were within the acceptable range; NfL showed at the highest used concentration some background binding to the C1 chip even in absence of capture antibody which could not be improved by testing various regeneration conditions
Summary
Cerebrospinal fluid (CSF) neurofilament light (NfL) is a reliable marker of neuro-axonal damage in different neurological disorders that is related to disease severity. To confirm the large body of evidence for NfL, we developed a new ELISA method and here we present the performance characteristics of this new ELISA for CSF NfL in different neurological disorders. Because of the widespread localization of NfL within the CNS, an increase in its concentration in the CSF is considered a general marker of neuro-axonal damage [5]. CSF NfL is a promising marker for identifying neurodegenerative diseases, reliably measuring the degree of the ongoing neuro-axonal damage, and defining the prognosis of several neurological diseases and the response to treatment with disease-modifying drugs [6]
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