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Neurofilament light chain in FTD is elevated not only in cerebrospinal fluid, but also in serum
  1. Carlo Wilke1,2,
  2. Oliver Preische2,3,
  3. Christian Deuschle1,2,
  4. Benjamin Roeben1,2,
  5. Anja Apel1,2,
  6. Christian Barro4,
  7. Luis Maia5,6,
  8. Walter Maetzler1,2,
  9. Jens Kuhle4,
  10. Matthis Synofzik1,2
  1. 1 Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
  2. 2 German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany
  3. 3 Department of Psychiatry, University of Tübingen, Tübingen, Germany
  4. 4 Neurology, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland
  5. 5 Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
  6. 6 Department of Neurology, Hospital de Santo António-CHP, Porto, Portugal
  1. Correspondence to Dr Matthis Synofzik, Department of Neurodegenerative Diseases, University of Tübingen Hoppe-Seyler-Str 3, Tübingen 72076, Germany; matthis.synofzik{at}uni-tuebingen.de

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Introduction

Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder for which readily available biomarkers are needed to monitor disease progression and response to future therapies. Neurofilament light chain (NfL), a cytoskeletal protein, is elevated in the cerebrospinal fluid (CSF) of patients with FTD, correlating with disease severity.1 ,2 As CSF sampling is more invasive than venepuncture and requires higher subject compliance, we tested the hypothesis that NfL levels in FTD are elevated not only in CSF, but also in serum. NfL levels in FTD were also compared with those in amyotrophic lateral sclerosis (ALS).3

Methods

CSF and serum samples of a consecutive series of 41 FTD, 25 ALS and 46 healthy control subjects were collected from 2009 until 2014 (see online supplement 1: Methodological and statistical details, see online supplement 2: Subject characteristics). Only participants with normal CSF white cell counts (cell count <5/µL) and normal CSF amyloid-β levels (amyloid-β-42 >600 pg/mL, Innotest ELISA, Innogenetics, Belgium) were included. CSF and serum NfL concentrations were measured by a previously established electrochemiluminescence immunoassay.4 CSF levels of total tau (h-tau) were determined by a commercial ELISA (Innogenetics).

Supplementary data

[jnnp-2015-312972supp.pdf]

Results

NfL levels in CSF differed significantly between FTD, ALS and control subjects (F (2, 109)=88.36, p<0.001, one-way analysis of variance (ANOVA), calculated for log-transformed levels, figure 1A), also if corrected for age (F (2, 108)=88.66, p<0.001). Both patients with FTD (2557 pg/mL (median); 1760–3167, (IQR)) and patients with ALS (6658 pg/mL; (4205–10438)) showed significantly higher CSF NfL levels than controls (981 pg/mL; (777–1374)). NfL levels in ALS were significantly higher than in FTD (all p<0.001, two-sided Student's t tests, Bonferroni-corrected, effect sizes: FTD vs controls r=0.65, ALS vs controls r=0.85, ALS vs FTD r=0.59).

Figure 1

(A) and (B) neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and serum of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and …

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