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, welldefined 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. Glossary Aβ42 = β-amyloid 1–42; AD = Alzheimer disease; AUC = area under the curve; bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; CDR = Clinical Dementia Rating; CDR-SB = Clinical Dementia Rating–Sum of Boxes; CI = confidence interval; CV = coefficient of variation; FAB = Frontal Assessment Battery; FTD = frontotemporal dementia; FTLD = frontotemporal lobar degeneration; FUS = fused in sarcoma; lvPPA = logopenic variant primary progressive aphasia; MMSE = Mini-Mental State Examination; MND = motor neuron disease; NfL = neurofilament light chain; nfvPPA = nonfluent variant primary progressive aphasia; PPA = primary progressive aphasia; PSP = progressive supranuclear palsy; p-tau = phosphorylated tau; svPPA = semantic variant primary progressive aphasia; TDP = TAR DNA-binding protein 43; t-tau = total tau.

Additional Metadata
Persistent URL dx.doi.org/10.1212/wnl.0000000000005261, hdl.handle.net/1765/114924
Journal Neurology
Citation
Meeter, L.H.H, Vijverberg, E.G., Del Campo, M, Rozemuller, A.J.M, Donker Kaat, L, de Jong, F.J, … Pijnenburg, Y.A.L. (2018). Clinical value of neurofilament and phospho-tau/tau ratio in the frontotemporal dementia spectrum. Neurology, 90(14), E1231–E123+. doi:10.1212/wnl.0000000000005261