Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep

Abstract

Scrapie is a fatal neurodegenerative disease of sheep and goats belonging to the group of Transmissible Spongiform Encephalopathy or prion diseases. The EU has adopted mandatory measures for scrapie surveillance to safeguard public and animal health because it is highly contagious and might decimate all genetic susceptible animals in affected flocks. Definite diagnosis of scrapie relies on the detection of the pathological prion protein in brain tissues and there are still no blood biomarkers available for making diagnosis in living animals that can be used for the screening of sheep in scrapie-affected flocks. Neurofilament light (NfL) protein, a valid biomarker for neuronal and axonal damages, can now be easily measured in blood by the ultra-sensitive single molecule array (Simoa) technology. Recent work reported that serum NfL is increased in neurodegenerative diseases, including human prion diseases, but no data are available for scrapie or other animal prion diseases. Here, we found that the median serum NfL concentration in scrapie animals (56.2, IQR 42.2–84.8, n = 9) was more than 15 times higher (p = 0.00084) than that found in control samples (3.4, IQR 3.0–26.3, n = 11). Moreover, serum NfL concentration in scrapie sheep with clinical signs (n = 2; 75.3, 15.7 pg/ml) did not significantly (p = 0.541; t-test) differ from scrapie animals without clinical signs (n = 7; 61.0, 10.7 pg/ml). The receiver operating characteristic (ROC) curve analysis estimated the cut-off value of 31 pg/ml serum NfL for distinguishing scrapie-infected sheep from controls. The application of this cut-off value gives an accuracy of the test of 95% (percent error of 5.23%). These data indicate that the Simoa test for serum NfL might be a useful screening method for detecting preclinical scrapie in living sheep. Finally, the preliminary data reported here need confirmation in large and more structured studies.

Network perturbation analysis in human bronchial epithelial cells following SARS-CoV2 infection

“…The area under the ROC curve (AUC) and its 95% confidence interval (95% CI) indicate diagnostic efficiency. The accuracy of the test with the percent error is reported [ 32 ].…”

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

“…Plasma pNfH levels also closely reflect later stages of disease progression and therapeutic response in the SOD1 (superoxide dismutase 1) G93A mouse model of ALS (Lu et al, 2012). Recently, serum NfL concentration in sheep with prion disease was more than 15 times higher than that found in control samples (Zetterberg et al, 2019). More recently, plasma NfL levels were also reported to reflect disease severity in mice inoculated with prions and fell significantly in antisense oligonucleotide-treated mice compared to the immediate pre-dose timepoint, suggesting a reversal of pathology driving the 53% increase in survival time (Minikel et al, 2020).…”

Neuroimmune Response in Natural Preclinical Scrapie after Dexamethasone Treatment

“…This is based on the fact that the mechanisms underlying cytokine release could be a crucial target for therapeutic approaches in the central nervous system (CNS) in prion diseases [25]. Several other studies examined very early time points in scrapie, but most of them used experimental models in rodents [26][27][28] or in sheep [29], with just a few of them having used the natural model of the disease [30][31][32]. To study natural field cases of scrapie is, in our opinion, essential, because they represent a more feasible source of knowledge than experimental models.…”