Serum NFL discriminates Parkinson disease from atypical parkinsonisms

Abstract

ObjectiveTo investigate the diagnostic value of serum neurofilament light chain (NFL) in patients with clear signs of parkinsonism but whose specific diagnosis was yet uncertain.MethodsSerum samples were collected from patients with clear signs of parkinsonism but with uncertain diagnosis at the inclusion. Clinical diagnoses of Parkinson disease (PD) and atypical parkinsonism disorders (APDs) were established after 3 years of follow-up and updated again after a maximum of 12 years in case longer follow-up data were available. Serum NFL was quantified by single molecule array in patients with PD (n = 55) and APD (n = 29, multiple system atrophy = 22, progressive supranuclear palsy = 7) and 53 nonneurologic controls.ResultsSerum NFL levels were elevated and differentiated the APD group (mean 23.8 ± 10.3 ng/L) from PD (mean 10.4 ± 4.9 ng/L) and controls (mean 11.5 ± 6.5 ng/L, p < 0.0001) with accuracy levels up to 91% (sensitivity = 86% and specificity = 85%). Serum NFL strongly correlated with CSF NFL levels (r = 0.72, p < 0.0001) in all groups and with age in PD (r = 0.78, p < 0.0001) and controls (r = 0.66, p < 0.0001). In our cohort, the probability of having APD was 76% (positive predictive value) and of having PD 92% (negative predictive value).ConclusionSerum NFL levels are markedly elevated in APD compared to PD and discriminate APDs from PD with high accuracy. Serum NFL may be a useful clinical biomarker to identify APD, even at stages when clinical symptoms are not yet conclusive.Classification of evidenceThis study provides Class II evidence that serum NFL levels accurately discriminate APDs from PD.

Diagnostic value of plasma neurofilament light: A multicentre validation study

“…While plasma NfL data from atypical parkinsonian patients in the Lund cohort has been previously reported 24,25 it is congruent with novel data included from the KCL cohort. In both cohorts, atypical parkinsonian disorders (e.g., CBS, PSP, MSA) had substantial increases in plasma NfL as compared to PD with very high diagnostic accuracies (KCL AUC > 86%; Lund AUC > 95%) and large effect sizes.…”

“…Interestingly, NfL is seemingly not elevated in Parkinson's disease (PD) in comparison to other neurodegenerative disorders and therefore a discrimination can be made from atypical parkinsonian disorders 24,25 . Furthermore, developing evidence demonstrates the potential use of using plasma NfL in discriminating FTD and primary psychiatric disorders 26,27 suggesting a potential differential diagnostic value of blood NfL in certain clinically relevant situations.…”

Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson’s Disease Progression

“…NfL levels have been shown to differentiate sporadic PD from other movement disorders, such as MSA and progressive supranuclear palsy (PSP). 7,12,13 While one small study did not show a longitudinal change in…”

Perspectives in fluid biomarkers in neurodegeneration from the 2019 biomarkers in neurodegenerative diseases course—a joint PhD student course at University College London and University of Gothenburg

“…CSF NfL level has been shown to differ between AD and other forms of dementia-for example, FTD patients exhibit significantly higher values of CSF NfL in comparison to AD patients, as reported in recent post-mortem study [47]. Serum NfL can also discriminate between idiopathic Parkinson's disease (PD) and atypical parkinsonism that is clinically indistinguishable at the stage of testing [48,49]. In Huntington's disease (HD), plasma NfL levels are closely associated with MRI brain volume and clinical severity and may be a useful outcome measure in tracking clinical response to disease-modifying therapies [50].…”