Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder

Great work by friends and colleagues on this paper the results within... however the most important question is whether NfL differentiates the really challenging cases from one another. For example, many neurologists would recognise 'text book' PD compared with one of the so-called Parkinson's plus disorder... a smaller number would recognise when there are atypical features in the patient with PD and would therefore try to characterise further or wait until time gave further clues... But there are some patients in which you just do not know. It could be PD or a mimic... it is for those patients that I would love to see a biomarker that really differentiates and I suspect the NfL is not specific enough and more than one marker may be required...

Neurology. 2017 Feb 8. pii: 10.1212/WNL.0000000000003680. doi: 10.1212/WNL.0000000000003680. [Epub ahead of print]
Hansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, Andreasson U, Norgren N, Linder J, Forsgren L, Constantinescu R, Zetterberg H, Blennow K; Swedish BioFINDER study.

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.