Abstract
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.
Highlights
Classification of evidence: This study provides Class III evidence that blood neurofilament light chain (NfL) levels discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD)
Our group and others have previously shown that the CSF concentration of NfL is increased in APD but not in PD3,4 and that NfL in CSF can discriminate between PD and APD with a high degree of diagnostic accuracy
In the Lund cohort, blood levels of NfL correlated with age in the whole cohort (r 5 0.449, p, 0.001), in controls (r 5 0.436, p 5 0.001), and in patients with PD (r 5 0.577, p, 0.001), but not in patients with APD (i.e., progressive supranuclear palsy (PSP), multiple system atrophy (MSA), or corticobasal syndrome (CBS))
Summary
The study included 3 independent prospective cohorts: the Lund (n 5 278) and London (n 5 117) 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 5 109) 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. The study was conducted in accordance with the Declaration of Helsinki and was approved by the regional ethical review boards in Lund, London, Umeå, and Gothenburg. All participants provided written informed consent to participate in the study. Our primary research question was to determine whether blood NfL can discriminate between PD and APD. The study provides Class III evidence that blood NfL levels discriminate between PD and APD with high diagnostic accuracy
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