Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep.
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0226697 |
| _version_ | 1818406652055912448 |
|---|---|
| author | Henrik Zetterberg Elena Bozzetta Alessandra Favole Cristiano Corona Maria Concetta Cavarretta Francesco Ingravalle Kaj Blennow Maurizio Pocchiari Daniela Meloni |
| author_facet | Henrik Zetterberg Elena Bozzetta Alessandra Favole Cristiano Corona Maria Concetta Cavarretta Francesco Ingravalle Kaj Blennow Maurizio Pocchiari Daniela Meloni |
| author_sort | Henrik Zetterberg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T09:15:20Z |
| format | Article |
| id | doaj.art-d6ef043515c2486a9c6bbc903b49426d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T09:15:20Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d6ef043515c2486a9c6bbc903b49426d2022-12-21T23:08:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011412e022669710.1371/journal.pone.0226697Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep.Henrik ZetterbergElena BozzettaAlessandra FavoleCristiano CoronaMaria Concetta CavarrettaFrancesco IngravalleKaj BlennowMaurizio PocchiariDaniela MeloniScrapie 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.https://doi.org/10.1371/journal.pone.0226697 |
| spellingShingle | Henrik Zetterberg Elena Bozzetta Alessandra Favole Cristiano Corona Maria Concetta Cavarretta Francesco Ingravalle Kaj Blennow Maurizio Pocchiari Daniela Meloni Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep. PLoS ONE |
| title | Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep. |
| title_full | Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep. |
| title_fullStr | Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep. |
| title_full_unstemmed | Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep. |
| title_short | Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep. |
| title_sort | neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep |
| url | https://doi.org/10.1371/journal.pone.0226697 |
| work_keys_str_mv | AT henrikzetterberg neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT elenabozzetta neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT alessandrafavole neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT cristianocorona neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT mariaconcettacavarretta neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT francescoingravalle neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT kajblennow neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT mauriziopocchiari neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep AT danielameloni neurofilamentsinbloodisanewpromisingpreclinicalbiomarkerforthescreeningofnaturalscrapieinsheep |