Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie

Authors: Lathrop, Quazetta; Nicholson, Eric; WANG, CHONG - Iowa State University; Greenlee, Justin; SEGER, HANNAH - Oak Ridge Institute For Science And Education (ORISE); Veneziano, Susan; Cassmann, Eric

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2024
Publication Date: 2/23/2024
Citation: Lathrop, Q.L., Nicholson, E.M., Wang, C., Greenlee, J.J., Seger, H., Veneziano, S.E., Cassmann, E.D. 2024. Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie. PLOS ONE. https://doi.org/10.1371/journal.pone.0299038.
DOI: https://doi.org/10.1371/journal.pone.0299038

Interpretive Summary: Scrapie is a prion disease that affects sheep and goats. There is not an easily accessible and rapid antemortem diagnostic test for prion diseases in livestock. We assessed the feasibility of using a blood sample to measure a biomarker called neurofilament light chain (Nf-L) as an indicator of brain damage. Previous research in humans has indicated that Nf-L may elevate in the blood years prior to symptom development. We sought to characterize the timeframe of Nf-L increases in sheep relative to the incubation period of scrapie. Serum Nf-L concentrations in our experimental sheep increased as scrapie progressed; however, Nf-L blood levels did not increase significantly before the animals showed neurologic symptoms. The Nf-L levels increased substantially throughout the final 10% of the animals’ scrapie incubation period when other clinical signs were present. We concluded that serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie. This information may be useful to researchers and veterinary diagnosticians.

Technical Abstract: Objective: Nf-L has been used to detect axonal damage in the brain by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for early detection of scrapie in sheep. Methods: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. After inoculation, blood was collected every 4 weeks until 44 weeks post-inoculation at which point weekly collection commenced. Blood was collected and centrifuged to separate serum, and the serum was analyzed using the Quanterix SR-X platform to evaluate Nf-L concentrations at each timepoint and at the time of euthanasia.