#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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
prolekare.web.journal.doi_sk: https://doi.org/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:

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


Zdroje

1. Johnson RT. Prion diseases. Lancet Neurol. 2005;4:635–42. doi: 10.1016/S1474-4422(05)70192-7 16168932

2. Houston F, Andréoletti O. Animal prion diseases: the risks to human health. Brain Pathol. 2019;29:248–62. doi: 10.1111/bpa.12696 30588682

3. Houston F, Andréoletti O. The zoonotic potential of animal prion diseases. Handb Clin Neurol. 2018;153:447–62. doi: 10.1016/B978-0-444-63945-5.00025-8 29887151

4. Cassard H, Torres JM, Lacroux C, Douet JY, Benestad SL, Lantier F, et al. Evidence for zoonotic potential of ovine scrapie prions. Nat Commun. 2014;5:5821. doi: 10.1038/ncomms6821 25510416

5. Baker HF, Ridley RM, Wells GA. Experimental transmission of BSE and scrapie to the common marmoset. Vet Rec. 1993;132:403–6. doi: 10.1136/vr.132.16.403 8488658

6. Comoy EE, Mikol J, Luccantoni-Freire S, Correia E, Lescoutra-Etchegaray N, Durand V, et al. Transmission of scrapie prions to primate after an extended silent incubation period. Sci Rep. 2015;5:11573. doi: 10.1038/srep11573 26123044

7. Gill AC, Castle AR. The cellular and pathologic prion protein. Handb Clin Neurol. 2018;153:21–44. doi: 10.1016/B978-0-444-63945-5.00002-7 29887138

8. Chianini F, Cosseddu GM, Steele P, Hamilton S, Hawthorn J, Síso S, et al. Correlation between infectivity and disease associated prion protein in the nervous system and selected edible tissues of naturally affected scrapie sheep. PLoS One. 2015;10:e0122785. doi: 10.1371/journal.pone.0122785 25807559

9. Zanusso G, Monaco S, Pocchiari M, Caughey B. Advanced tests for early and accurate diagnosis of Creutzfeldt-Jakob disease. Nat Rev Neurol. 2016;12:325–33. doi: 10.1038/nrneurol.2016.65 27174240

10. Mackenzie G, Will R. Creutzfeldt-Jakob disease: recent developments. F1000Res. 2017;6:2053. doi: 10.12688/f1000research.12681.1 29225787

11. Kramm C, Pritzkow S, Lyon A, Nichols T, Morales R, Soto C. Detection of Prions in Blood of Cervids at the Asymptomatic Stage of Chronic Wasting Disease. Sci Rep. 2017;7:17241. doi: 10.1038/s41598-017-17090-x 29222449

12. Concha-Marambio L, Pritzkow S, Moda F, Tagliavini F, Ironside JW, Schulz PE, et al. Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease. Sci Transl Med. 2016;8:370ra183. doi: 10.1126/scitranslmed.aaf6188 28003548

13. Bougard D, Brandel JP, Bélondrade M, Béringue V, Segarra C, Fleury H, et al. Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease. Sci Transl Med. 2016;8:370ra182. doi: 10.1126/scitranslmed.aag1257 28003547

14. Castilla J, Saá P, Soto C. Detection of prions in blood. Nat Med. 2005;11:982–5. doi: 10.1038/nm1286 16127436

15. Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L, et al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol. 2010;28:595–9. doi: 10.1038/nbt.1641 20495550

16. Gisslén M, Price RW, Andreasson U, Norgren N, Nilsson S, Hagberg L, et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine 2015;3:135–140. doi: 10.1016/j.ebiom.2015.11.036 26870824

17. Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, et al. Neurofilaments as promising biomarkers in neurological disorders. Nat Rev Neurol 2018;14:577–89. doi: 10.1038/s41582-018-0058-z 30171200

18. Acutis PL, Sbaiz L, Verburg F, Riina MV, Ru G, Moda G, et al. Low frequency of the scrapie resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed. J Gen Virol. 2004; 85:3165–72. doi: 10.1099/vir.0.80053-0 15448380

19. Mazza M, Iulini B, Vaccari G, Acutis PL, Martucci F, Esposito E, et al. Co-existence of classical scrapie and Nor98 in a sheep from an Italian outbreak. Res Vet Sci. 2010;88:478–85. doi: 10.1016/j.rvsc.2009.11.015 20031179

20. European Food Safety Authority. Scientific report of the European Food Safety Authority on the evaluation of rapid post mortem TSE tests intended for small ruminants. Adopted on 17 May 2005. EFSA J 2005;31:1–17. Question No. EFSA-Q-2003-084.

21. European Food Safety Authority. Scientific Opinion on the evaluation of new TSE rapid tests submitted in the framework of the Commission Call for expression of interest 2007/S204-247339. Adopted on 19 April 2012. Question No EFSA-Q-2008-327/455/456/457/458/459/460,.

22. Staffaroni AM, Kramer AO, Casey M, Kang H, Rojas JC, Orrú CD, et al. Association of Blood and Cerebrospinal Fluid Tau Level and Other Biomarkers With Survival Time in Sporadic Creutzfeldt-Jakob Disease. JAMA Neurol. 2019 May 6 doi: 10.1001/jamaneurol.2019.1071 [Epub ahead of print] 31058916

23. Thompson AGB, Luk C, Heslegrave AJ, Zetterberg H, Mead SH, Collinge J, et al. Neurofilament light chain and tau concentrations are markedly increased in the serum of patients with sporadic Creutzfeldt-Jakob disease, and tau correlates with rate of disease progression. J Neurol Neurosurg Psychiatry. 2018;89:955–61. doi: 10.1136/jnnp-2017-317793 29487167

24. Kovacs GG, Andreasson U, Liman V, Regelsberger G, Lutz MI, Danics K, et al. Plasma and cerebrospinal fluid tau and neurofilament concentrations in rapidly progressive neurological syndromes: a neuropathology-based cohort. Eur J Neurol. 2017;24:1326–e77. doi: 10.1111/ene.13389 28816001

25. Steinacker P, Blennow K, Halbgebauer S, Shi S, Ruf V, Oeckl P, et al. Neurofilaments in blood and CSF for diagnosis and prediction of onset in Creutzfeldt-Jakob disease. Sci Rep. 2016;6:38737. doi: 10.1038/srep38737 27929120

26. Lewczuk P, Riederer P, O'Bryant SE, Verbeek MM, Dubois B, Visser PJ, et al. Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry. 2018;19:244–328. doi: 10.1080/15622975.2017.1375556 29076399

27. Bacioglu M, Maia LF, Preische O, Schelle J, Apel A, Kaeser SA, et al. Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases. Neuron. 2016;91:56–66. doi: 10.1016/j.neuron.2016.05.018 27292537

28. Clement A, Mitchelmore C, Andersson DR, Asuni AA. Cerebrospinal fluid neurofilament light chain as a biomarker of neurodegeneration in the Tg4510 and MitoPark mouse models. Neuroscience. 2017;354:101–109. doi: 10.1016/j.neuroscience.2017.04.030 28461218

29. Soylu-Kucharz R, Sandelius Å, Sjögren M, Blennow K, Wild EJ, Zetterberg H, et al. Neurofilament light protein in CSF and blood is associated with neurodegeneration and disease severity in Huntington's disease R6/2 mice. Sci Rep. 2017;7:14114. doi: 10.1038/s41598-017-14179-1 29074982

30. Zerr I, Schmitz M, Karch A, Villar-Piqué A, Kanata E, Golanska E, et al. Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases. Alzheimers Dement. 2018;14:751–763. doi: 10.1016/j.jalz.2017.12.008 29391125

31. Abu-Rumeileh S, Capellari S, Stanzani-Maserati M, Polischi B, Martinelli P, Caroppo P, et al. The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias. Alzheimers Res Ther. 2018;10:3. doi: 10.1186/s13195-017-0331-1 29368621

32. Ladogana A, Puopolo M, Croes EA, Budka H, Jarius C, Collins S, et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology. 2005;64:1586–91. doi: 10.1212/01.WNL.0000160117.56690.B2 15883321

33. Ligios C, Viglietti A, Carta P, Dexter G, Agrimi U, Simmons MM. Clinicopathological findings in sheep from Sardinia showing neurological signs of disease. Vet Rec. 2004;154:365–70. doi: 10.1136/vr.154.12.365 15074327

34. Polizopoulou SZ, Giadinis DN, Papahristou A, Papaioannou N. Neurological diseases of small ruminants in Greece: a retrospective study in 114 flocks. Acta Veterinaria-Beograd. 2016: 66:160–71.

35. Llorens F, Barrio T, Correia Â, Villar-Piqué A, Thüne K, Lange P, et al. Cerebrospinal Fluid Prion Disease Biomarkers in Pre-clinical and Clinical Naturally Occurring Scrapie. Mol Neurobiol. 2018;55:8586–8591. doi: 10.1007/s12035-018-1014-z 29572672

36. Preische O, Schultz SA, Apel A, Kuhle J, Kaeser SA, Barro C, et al. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease. Nat Med. 2019;25:277–283. doi: 10.1038/s41591-018-0304-3 30664784

37. van der Ende EL, Meeter LH, Poos JM, Panman JL, Jiskoot LC, Dopper EGP, et al. Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study. Lancet Neurol. 2019;18:1103–1111. doi: 10.1016/S1474-4422(19)30354-0 31701893

38. Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE. Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis. JAMA Neurol. 2019; 76:1035–1048.

39. Greenlee JJ. Review: Update on Classical and Atypical Scrapie in Sheep and Goats. Vet Pathol. 2019;56:6–16. doi: 10.1177/0300985818794247 30200819


Článok vyšiel v časopise

PLOS One


2019 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#