Plasma neurofilament light chain as a biomarker for fatal familial insomnia
Peter Hermann1, Sezgi Canaslan1, Anna Villar-Piqué2,3
1Department of Neurology, National Reference Center for CJD Surveillance, Göttingen University Medical Center, Göttingen, Germany.
Background And Purpose:
Fatal familial insomnia is a rare hereditary prion disease associated with the D178N-129M PRNP mutation. Early diagnosis is difficult, because the clinical syndrome may overlap with affective disorders. In addition, most known cerebrospinal fluid biomarkers for prion diseases and magnetic resonance imaging do not show a good diagnostic accuracy for fatal familial insomnia. In this context, data on plasma biomarkers are scarce.
Methods:
We analyzed levels of neurofilament light chain, glial fibrillary acidic protein, chitinase-3-like protein 1, calcium-binding protein B, and total tau protein in six serial plasma samples from a patient with fatal familial insomnia. Subsequently, plasma neurofilament light chain was analyzed in n = 25 patients and n = 19 controls. The diagnostic accuracy and associations with disease stage and duration were explored.
Results:
Among all biomarker candidates in the case study, only neurofilament light chain levels showed a constant evolution and increased over time. They discriminated fatal familial insomnia from controls with an area under the curve of 0.992 (95% confidence interval [CI] = 0.974-1) in the case-control study. Higher concentrations were associated with methionine homozygosity at codon 129 PRNP (p = 0.006), shorter total disease duration (rho = -0.467, p = 0.019, 95% CI = -0.790 to -0.015), and shorter time from sampling to death (rho = -0.467, p = 0.019, 95% CI = -0.773 to -0.019).
Conclusions:
Plasma neurofilament light chain may be a valuable minimally invasive diagnostic biomarker for fatal familial insomnia after clinical onset. Most important, stage-related increase and association with disease duration indicate potential as a prognostic marker and as a surrogate marker in clinical trials.
Insights
Plasma neurofilament light chain shows promise as a diagnostic and prognostic biomarker for fatal familial insomnia. This prion disease biomarker
Area of Science:
- Neurology
- Prion Diseases
- Biomarker Discovery
Background:
- Fatal familial insomnia (FFI) is a rare, inherited prion disease.
- Diagnostic challenges arise from overlapping symptoms with affective disorders.
- Current diagnostic tools like CSF biomarkers and MRI have limited accuracy for FFI.
Purpose of the Study:
- To investigate plasma biomarkers for diagnosing fatal familial insomnia.
- To assess the potential of neurofilament light chain (NfL) as a diagnostic and prognostic marker for FFI.
Main Methods:
- Analyzed serial plasma samples from an FFI patient for multiple biomarkers.
- Focused on plasma neurofilament light chain (NfL) in 25 FFI patients and 19 controls.
- Evaluated NfL's diagnostic accuracy and correlation with disease stage and duration.
Main Results:
- Plasma NfL levels consistently increased over time in the FFI patient.
- NfL demonstrated high diagnostic accuracy (AUC = 0.992) in distinguishing FFI from controls.
- Elevated NfL correlated with PRNP codon 129 methionine homozygosity and shorter disease duration.
Conclusions:
- Plasma NfL is a potential minimally invasive diagnostic biomarker for FFI post-clinical onset.
- The stage-related increase and association with disease duration suggest NfL's prognostic value.
- NfL may serve as a surrogate marker in future clinical trials for FFI.
