Diagnostic value of cerebrospinal fluid tau, neurofilament, and progranulin in definite frontotemporal lobar degeneration

Alzheimers Res Ther. 2018 Mar 20;10(1):31. doi: 10.1186/s13195-018-0364-0.


Background: We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes.

Methods: CSF levels of routine AD biomarkers (phosphorylated tau (p-tau181), total tau (t-tau), and amyloid-beta (Aβ)1-42) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20). FTLD subgroups were defined by genetic carrier status and/or postmortem neuropathological confirmation (FTLD-TDP: n = 34, including FTLD-C9orf72: n = 19 and FTLD-GRN: n = 9; FTLD-tau: n = 10).

Results: GRN mutation carriers had significantly lower progranulin levels compared to other FTLD patients, AD, and controls. Both t-tau and p-tau181 were normal in FTLD patients, even in FTLD-tau. Aβ1-42 levels were very variable in FTLD. Neurofilament light chain (Nf-L) was significantly higher in FTLD compared with AD and controls. The reference logistic regression model based on the established AD biomarkers could be improved by the inclusion of CSF Nf-L, which was also important for the differentiation between FTLD and controls. Within the FTLD cohort, no significant differences were found between FTLD-TDP and FTLD-tau, but GRN mutation carriers had higher t-tau and Nf-L levels than C9orf72 mutation carriers and FTLD-tau patients.

Conclusions: There is an added value for Nf-L in the differential diagnosis of FTLD. Progranulin levels in CSF depend on mutation status, and GRN mutation carriers seem to be affected by more severe neurodegeneration.

Keywords: Alzheimer’s disease; Biomarkers; Cerebrospinal fluid; Differential diagnosis; Frontotemporal lobar degeneration; Neurofilament; Progranulin; Tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Cohort Studies
  • Female
  • Frontotemporal Lobar Degeneration / cerebrospinal fluid*
  • Frontotemporal Lobar Degeneration / diagnosis*
  • Frontotemporal Lobar Degeneration / genetics
  • Humans
  • Intermediate Filaments / metabolism*
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Progranulins / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*


  • Progranulins
  • tau Proteins