| 1. |
- Gaetani, L., et al.
(author)
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A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation
- 2018
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In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
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Journal article (peer-reviewed)abstract
- Background: 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 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. Methods: We 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). Results: Our 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. Conclusions: These 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.
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| 2. |
- Gaetani, Lorenzo, et al.
(author)
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Cerebrospinal fluid neurofilament light chain predicts disease activity after the first demyelinating event suggestive of multiple sclerosis
- 2019
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In: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 35, s. 228-232
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Journal article (peer-reviewed)abstract
- Background: The prediction of disease activity in patients with a first demyelinating event suggestive of multiple sclerosis (MS) is of high clinical relevance. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has shown to have prognostic value in MS patients. In this work, we measured CSF NfL in patients at the first demyelinating event in order to find a cut-off value able to discriminate patients who will have disease activity from those who will remain stable during the follow-up. Methods: We included CSF samples collected within 30 days after the onset of the first demyelinating event from 32 patients followed-up for 3.8 ± 2.5 years. CSF NfL was measured with a newly developed in-house enzyme linked immunosorbent assay (ELISA). Results: At the first demyelinating event, patients with subsequent disease activity had significantly higher baseline CSF NfL values compared to clinically and radiologically stable patients (median 812.5 pg/mL, range 205–2359 pg/mL vs 329.5 pg/mL, range 156–3492 pg/mL, p = 0.002). A CSF NfL cut-off value of 500 pg/mL significantly discriminated these two groups of patients with a 90% sensitivity and an 83.3% specificity. Conclusion: Our results confirm that CSF NfL is a prognostic marker in the very early phases of MS. The validation of a cut-off value of 500 pg/mL could provide clinicians with a dichotomous variable that can simplify the prognostic assessment of patients at the first demyelinating event.
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| 3. |
- Gaetani, L., et al.
(author)
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Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis
- 2019
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In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:9, s. 2157-2163
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Journal article (peer-reviewed)abstract
- Background Cognitive impairment (CI) is a disabling symptom of multiple sclerosis (MS). Axonal damage disrupts neural circuits and may play a role in determining CI, but its detection and monitoring are not routinely performed. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a promising marker of axonal damage in MS. Objective To retrospectively examine the relationship between CSF NfL and CI in MS patients. Methods CSF NfL concentration was measured in 28 consecutive newly diagnosed MS patients who underwent a neuropsychological evaluation with the Brief Repeatable Battery of Neuropsychological tests (BRBN). Results CSF NfL was higher in patients with overall CI (947.8 +/- 400.7 vs 518.4 +/- 424.7 pg/mL, p < 0.01), and with impairment in information processing speed (IPS) (820.8 +/- 413.6 vs 513.6 +/- 461.4 pg/mL, p < 0.05) and verbal fluency (1292 +/- 511 vs 582.8 +/- 395.4 pg/mL, p < 0.05), and it positively correlated with the number of impaired BRBN tests (r = 0.48, p = 0.01) and cognitive domains (r = 0.47, p = 0.01). Multivariate analyses taking into account potential confounders confirmed these findings. Conclusion CSF NfL is higher in MS patients with CI and impaired IPS and verbal fluency. Large myelinated axons injury, causing neural disconnection, may be an important determinant of CI in MS and can be reliably measured through CSF NfL.
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