Molecular Neurobiology | June 18, 2022
Matthias Schmitz, Sezgi Canaslan, Juan Carlos Espinosa, Natalia Fernández-Borges, Anna Villar-Piqué, Franc Llorens, Daniela Varges, Fabian Maass, Juan Maria Torres, Peter Hermann & Inga Zerr
Molecular Neurobiology volume 59, pages1–9 (2022)
https://doi.org/10.1007/s12035-022-02891-7
Biomarkers are becoming increasingly important for the differential diagnosis of neurodegenerative diseases. Previous observations indicated neurofilament light chain (NfL) as a potential blood-based biomarker for sporadic Creutzfeldt-Jakob disease (sCJD). Here, we investigated the stability, inter-assay/intra-assay variation and the regulation of NfL levels in CSF and plasma in a large cohort of sCJD patients by using a single-molecule array (SIMOA). We defined cutoffs for an accurate diagnosis and measured plasma NfL level in prion-infected mice models at different time points to identify the potential dynamics throughout the disease. Our analyses confirmed CSF and plasma NfL as stable and consistent marker for sCJD. Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.92–0.93 to distinguish sCJD from control groups. Newly defined cutoffs revealed good diagnostic accuracies of CSF and plasma NfL, indicated by a sensitivity of 80–83.5% and a specificity of 87.4–91%. Studies on two humanized prion-infected mice lines (Tg340-PRNP 129MM and Tg361-PRNP 129VV) revealed increased plasma NfL levels in a late pre-clinical or very early clinical stage between 120–150 days post-inoculation. In conclusion, our work supports the potential use of CSF and plasma NfL as a very early biomarker in sCJD diagnostic with good diagnostic accuracies.
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