%X Delayed diagnosis and misdiagnosis are frequent in people with amyotrophic lateral sclerosis
(ALS), the most common form of motor neuron disease (MND). Neurofilament light chain (NFL) and
phosphorylated neurofilament heavy chain (pNFH) are elevated in ALS patients. We retrospectively
quantified cerebrospinal fluid (CSF) NFL, CSF pNFH and plasma NFL in stored samples that were
collected at the diagnostic work-up of ALS patients (n = 234), ALS mimics (n = 44) and controls (n = 9).
We assessed the diagnostic performance, prognostication value and relationship to the site of onset
and genotype. CSF NFL, CSF pNFH and plasma NFL levels were significantly increased in ALS patients
compared to patients with neuropathies & myelopathies, patients with myopathies and controls.
Furthermore, CSF pNFH and plasma NFL levels were significantly higher in ALS patients than in
patients with other MNDs. Bulbar onset ALS patients had significantly higher plasma NFL levels
than spinal onset ALS patients. ALS patients with C9orf72HRE mutations had significantly higher
plasma NFL levels than patients with SOD1 mutations. Survival was negatively correlated with all
three biomarkers. Receiver operating characteristics showed the highest area under the curve for CSF
pNFH for differentiating ALS from ALS mimics and for plasma NFL for estimating ALS short and long
survival. All three biomarkers have diagnostic value in differentiating ALS from clinically relevant ALS
mimics. Plasma NFL levels can be used to differentiate between clinical and genetic ALS subgroups.
%L discovery10138467
%I Springer Science and Business Media LLC
%O This article is licensed under a Creative Commons Attribution 4.0 International
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%A A Behzadi
%A F Pujol-Calderón
%A AE Tjust
%A A Wuolikainen
%A K Höglund
%A K Forsberg
%A E Portelius
%A K Blennow
%A H Zetterberg
%A PM Andersen
%J Scientific Reports
%V 11
%T Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics
%N 1
%D 2021