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

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

Joery Goossens  1   2 , Maria Bjerke  1   2 , Sara Van Mossevelde  2   3   4   5 , Tobi Van den Bossche  2   3   4   5 , Johan Goeman  4 , Bart De Vil  2   6 , Anne Sieben  2   3 , Jean-Jacques Martin  2 , Patrick Cras  2   5   6 , Peter Paul De Deyn  1   2   4 , Christine Van Broeckhoven  2   3 , Julie van der Zee  2   3 , Sebastiaan Engelborghs  7   8   9
Affiliations

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

Joery Goossens et al. Alzheimers Res Ther. .

Abstract

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.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the ethics committee of the University of Antwerp, Antwerp, Belgium (B300201420405). Informed consent was obtained from all subjects.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Dot plots of progranulin levels in all different (sub)groups. Values are presented as median and interquartile range. Left panels compare controls (triangles), Alzheimer’s disease (AD; squares), and frontotemporal lobar degeneration (FTLD; circles) dementia groups. Right panels compare FTLD subgroups: FTLD-TDP (triangles, squares (representing FTLD-C9orf72 symptomatic mutation carriers), and circles (representing FTLD-GRN symptomatic mutation carriers)), and FTLD-tau (downward triangles)). The dotted line represents the median control level, and the dashed line represents the median AD level. ***p < 0.001, **p < 0.01, *p < 0.05. CSF cerebrospinal fluid, ns not significant
Fig. 2
Fig. 2
Dot plots of AD CSF biomarkers in all different (sub)groups. Values are presented as median and interquartile range. Left panels compare controls (triangles), Alzheimer’s disease (AD; squares), and frontotemporal lobar degeneration (FTLD; circles) dementia groups. Right panels compare FTLD subgroups: FTLD-TDP (triangles, squares (representing FTLD-C9orf72 symptomatic mutation carriers), and circles (representing FTLD-GRN symptomatic mutation carriers)), and FTLD-tau (downward triangles)). The dotted line represents the median control level, and the dashed line represents the median AD level. ***p < 0.001, **p < 0.01, *p < 0.05. Aβ amyloid-beta, ns not significant, p-tau181 phosphorylated tau, t-tau total tau
Fig. 3
Fig. 3
Dot plots of neurofilament protein levels in all different (sub)groups. Values are presented as median and interquartile range. Left panels compare controls (triangles), Alzheimer’s disease (AD; squares), and frontotemporal lobar degeneration (FTLD; circles) dementia groups. Right panels compare FTLD subgroups: FTLD-TDP (triangles, squares (representing FTLD-C9orf72 symptomatic mutation carriers), and circles (representing FTLD-GRN symptomatic mutation carriers)), and FTLD-tau (downward triangles)). The dotted line represents the median control level, and the dashed line represents the median AD level. ***p < 0.001, **p < 0.01, *p < 0.05. Nf-L neurofilament light chain, ns not significant, pNF-H phosphorylated neurofilament heavy chain
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