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


Autoři: Henrik Zetterberg aff001;  Elena Bozzetta aff005;  Alessandra Favole aff005;  Cristiano Corona aff005;  Maria Concetta Cavarretta aff005;  Francesco Ingravalle aff005;  Kaj Blennow aff001;  Maurizio Pocchiari aff006;  Daniela Meloni aff005
Působiště autorů: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden aff001;  Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden aff002;  Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom aff003;  UK Dementia Research Institute at UCL, University College London, London, United Kingdom aff004;  Istituto zooprofilattico del Piemonte Liguria e Valle d’Aosta, Turin, Italy aff005;  Department of Neuroscience, Istituto Superiore di Sanità, Roma, Italy aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226697

Souhrn

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.

Klíčová slova:

Animal prion diseases – Biomarkers – Blood – Cerebrospinal fluid – Diagnostic medicine – Scrapie – Sheep – Veterinary diseases


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Článek vyšel v časopise

PLOS One


2019 Číslo 12