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Multicenter Study
. 2017 Mar 7;88(10):930-937.
doi: 10.1212/WNL.0000000000003680. Epub 2017 Feb 8.

Blood-based NfL: A Biomarker for Differential Diagnosis of Parkinsonian Disorder

Free PMC article
Multicenter Study

Blood-based NfL: A Biomarker for Differential Diagnosis of Parkinsonian Disorder

Oskar Hansson et al. Neurology. .
Free PMC article


Objective: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders.

Methods: The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated.

Results: We found strong correlations between blood and CSF concentrations of NfL (ρ ≥ 0.73-0.84, p ≤ 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p < 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81).

Conclusions: Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics.

Classification of evidence: This study provides Class III evidence that blood NfL levels discriminate between PD and APD.


Figure 1
Figure 1. Correlations between blood and CSF levels of neurofilament light chain (NfL)
Blood and CSF NfL concentrations were measured in the Lund (A) and London (B) cohorts. NfL measurements of matched CSF samples were available for 245 participants in the Lund cohort (147 Parkinson disease [PD], 28 multiple system atrophy [MSA], 15 progressive supranuclear palsy [PSP], 5 corticobasal syndrome [CBS], and 50 controls) and 97 participants in the London cohort (5 PD, 29 MSA, 26 PSP, 11 CBS, and 26 controls).
Figure 2
Figure 2. Blood neurofilament light chain (NfL) in different diagnostic groups
Blood concentrations of NfL in the Lund (A), London (B), and early disease (C) cohorts; p values are from univariate general linear models adjusting for age and sex; *p < 0.05; **p < 0.01; ***p < 0.001. One progressive supranuclear palsy (PSP) case in the early disease cohort with NfL concentration of 134.3 pg/mL is not shown in C (but was included in all statistical analysis). CBS = corticobasal syndrome; MSA = multiple system atrophy; PD = Parkinson disease.
Figure 3
Figure 3. Receiver operating characteristic (ROC) curves of blood neurofilament light chain (NfL)
ROC curves of blood NfL to distinguish Parkinson disease (PD) from atypical parkinsonian disorders (APD) (progressive supranuclear palsy [PSP], multiple system atrophy [MSA], and corticobasal degeneration [CBD]) in the Lund (A), London (B) and early disease (C) cohorts. The early disease cohort included 2 patient groups that were recruited in Göteborg and Umeå, respectively (e-Methods). ROC analysis produced similar results when diagnostic accuracy of blood NfL for differentiating PD from APD was assessed in Göteborg (area under the curve [AUC] 0.80) and Umeå (AUC = 0.81) patients separately.

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