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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
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).
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).