CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis (original) (raw)
Related papers
Frontiers in Aging Neuroscience
Background: Neurofilament light chain (NfL) is a validated biofluid marker of neuroaxonal damage with great potential for monitoring patients with neurodegenerative diseases. We aimed to further validate the clinical utility of plasma (p) vs. CSF (c) NfL for distinguishing patients with Amyotrophic Lateral Sclerosis (ALS) from ALS mimics. We also assessed the association of biomarker values with clinical variables and survival and established the longitudinal changes of pNfL during the disease course.Methods: We studied 231 prospectively enrolled patients with suspected ALS who underwent a standardized protocol including neurological examination, electromyography, brain MRI, and lumbar puncture. Patients who received an alternative clinical diagnosis were considered ALS mimics. We classified the patients based on the disease progression rate (DPR) into fast (DPR > 1), intermediate (DPR 0.5–1), and slow progressors (DPR < 0.5). All patients were screened for the most frequent A...
Journal of Neurochemistry, 2002
In the present study we describe an ELISA to quantify the light subunit of the neurofilament triplet protein (NFL) in CSF. The method was validated by measuring CSF NFL concentrations in healthy individuals and in two well-characterized groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). The levels were increased in ALS (1,743~1,661 ng/L; mean ± SD) and AD (346 ± 176 ng/L) compared with controls (138 ± 31 ng/L; p < 0.0001 for both). Within the ALS group, patients with lower motor neuron signs only had lower NFL levels (360 ± 237 ng/L) than those with signs of upper motor neuron disease (2,435 ± 1,633 ng/L) (p <0.05). In a second study patients with miscellaneous neurodegenerative diseases were investigated (vascular dementia, olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral infarctions, and multiple sclerosis), and the CSF NFL level was found to be increased (665 ± 385 ng/L; p < 0.0001). NFL is a main structural protein of axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in general, but particularly in ALS with involvement of the pyramidal tract.
Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis
Neurology, 2018
To examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS). We measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset ≤6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures. NfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS (< 0.0001). CSF and serum NfL and CSF pNfH discriminated patients with ALS with early symptom onset from those with other neurologic diseases and MND mimics with high sensitivity (94%, 88%, 98%, and 89%, 100%...
Diagnostic and Prognostic Performance of Neurofilaments in ALS
Frontiers in Neurology
There is a need for biomarkers for amyotrophic lateral sclerosis (ALS), to support the diagnosis of the disease, to predict disease progression and to track disease activity and treatment responses. Over the last decade multiple studies have investigated the potential of neurofilament levels, both in cerebrospinal fluid and blood, as biomarker for ALS. The most widely studied neurofilament subunits are neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH). Neurofilament levels are reflecting neuronal injury and therefore potentially of value in ALS and other neurological disorders. In this mini-review, we summarize and discuss the available evidence about neurofilaments as diagnostic and prognostic biomarker for human ALS.
Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS
Neurology, 2020
ObjectiveTo identify preferred neurofilament assays and clinically validate serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) as prognostic and potential pharmacodynamic biomarkers relevant to amyotrophic lateral sclerosis (ALS) therapy development.MethodsIn this prospective, multicenter, longitudinal observational study of patients with ALS (n = 229), primary lateral sclerosis (n = 20), and progressive muscular atrophy (n = 11), biological specimens were collected, processed, and stored according to strict standard operating procedures (SOPs). Neurofilament assays were performed in a blinded manner by independent contract research organizations.ResultsFor serum NfL and pNfH measured using the Simoa assay, there were no missing data (i.e., technical replicates below the lower limit of detection were not encountered). For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ∼4% and ∼10% of serum samples, respectively. Mean coeffici...
Validation of Serum Neurofilaments as Prognostic Potential Pharmacodynamic Biomarkers for ALS
2019
ObjectiveIdentify preferred neurofilament assays, and clinically validate serum NfL and pNfH as prognostic and potential pharmacodynamic biomarkers relevant to ALS therapy development.MethodsProspective, multi-center, longitudinal observational study of patients with ALS (n=229), primary lateral sclerosis (PLS, n=20) and progressive muscular atrophy (PMA, n=11). Biological specimens were collected, processed and stored according to strict standard operating procedures (SOPs) 1. Neurofilament assays were performed in a blinded manner by independent contract research organizations (CROs).ResultsFor serum NfL and pNfH measured using the Simoa assay, missing data (i.e. both technical replicates below the lower limit of detection (LLD) was not encountered. For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ∼4% and ∼10% of serum samples respectively. Mean coefficients of variation (CVs) for pNfH in serum and CSF were ∼4-5% and ∼2-3% respectively in all assay...
Amyotrophic lateral sclerosis & frontotemporal degeneration, 2017
Background: Neutrophil gelatinase-associated lipocalin (NGAL) exists as monomers, homodimers, and NGAL/matrix metalloproteinase-9 (MMP-9) complexes. Circulating neutrophils are activated in ongoing disseminated intravascular coagulation (DIC); therefore, plasma NGAL levels are likely to be increased in DIC. We investigated the diagnostic performance of the plasma NGAL level in predicting acute kidney injury (AKI) in patients with DIC and determined the prognostic value of NGAL. Methods: A total of 126 patients with suspected DIC were enrolled. The plasma free NGAL was analyzed with a point-of-care immunoassay. Plasma total NGAL and NGAL/MMP-9 complex levels were measured using commercial kits. Results: Median free and total NGAL levels were markedly higher in patients with AKI than those without AKI. However, no significant difference in the NGAL/MMP-9 complex level was found between the groups. In patients without AKI, the plasma free and total NGAL levels were significantly higher in those with overt-DIC than in those without overt-DIC. Of note, the free NGAL level showed a significant prognostic value in DIC. Conclusion: Plasma free and total NGAL proved to be powerful markers for AKI in DIC patients and plasma free NGAL also has a prognostic relevance in DIC patients without AKI.