Clinical value of neurofilament and phospho-tau/tau ratio in the frontotemporal dementia spectrum

Neurology. 2018 Apr 3;90(14):e1231-e1239. doi: 10.1212/WNL.0000000000005261. Epub 2018 Mar 7.


Objective: To examine the clinical value of neurofilament light chain (NfL) and the phospho-tau/total tau ratio (p/t-tau) across the entire frontotemporal dementia (FTD) spectrum in a large, well-defined cohort.

Methods: CSF NfL and p/t-tau levels were studied in 361 patients with FTD: 179 behavioral variant FTD, 17 FTD with motor neuron disease (FTD-MND), 36 semantic variant primary progressive aphasia (PPA), 19 nonfluent variant PPA, 4 logopenic variant PPA (lvPPA), 42 corticobasal syndrome, and 64 progressive supranuclear palsy. Forty-five cognitively healthy controls were also included. Definite pathology was known in 68 patients (49 frontotemporal lobar degeneration [FTLD]-TDP, 18 FTLD-tau, 1 FTLD-FUS).

Results: NfL was higher in all diagnoses, except lvPPA (n = 4), than in controls, equally elevated in behavioral variant FTD, semantic variant PPA, nonfluent variant PPA, and corticobasal syndrome, and highest in FTD-MND. The p/t-tau was lower in all clinical groups, except lvPPA, than in controls and lowest in FTD-MND. NfL did not discriminate between TDP and tau pathology, while the p/t-tau ratio had a good specificity (76%) and moderate sensitivity (67%). Both high NfL and low p/t-tau were associated with poor survival (hazard ratio on tertiles 1.7 for NfL, 0.7 for p/t-tau).

Conclusion: NfL and p/t-tau similarly discriminated FTD from controls, but not between clinical subtypes, apart from FTD-MND. Both markers predicted survival and are promising monitoring biomarkers for clinical trials. Of note, p/t-tau, but not NfL, was specific to discriminate TDP from tau pathology in vivo.

Classification of evidence: This study provides Class III evidence that for patients with cognitive issues, CSF NfL and p/t-tau levels discriminate between those with and without FTD spectrum disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aphasia, Primary Progressive / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Frontotemporal Dementia / cerebrospinal fluid*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Motor Neuron Disease / cerebrospinal fluid
  • Neurofilament Proteins / cerebrospinal fluid*
  • Phosphorylation
  • Prognosis
  • Sensitivity and Specificity
  • Supranuclear Palsy, Progressive / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid*


  • Biomarkers
  • MAPT protein, human
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins