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

Journal Article · Fri Feb 23 00:00:00 EST 2024 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0299038· OSTI ID:2469776

Brown, Quazetta ^[1]; Nicholson, Eric ^[2]; Wang, Chong ^[3]; Greenlee, Justin ^[2]; Seger, Hannah ^[1]; Veneziano, Susan ^[2]; Cassmann, Eric ^[2]

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1. US Dept. of Agriculture (USDA), Ames, IA (United States); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States); Iowa State Univ., Ames, IA (United States)
2. US Dept. of Agriculture (USDA), Ames, IA (United States)
3. Iowa State Univ., Ames, IA (United States)

Objective: Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. Methods: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. Results: Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrP^Sc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Conclusion: Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals’ scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

• Research Organization: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE Office of Science (SC)
• Grant/Contract Number: SC0014664
• OSTI ID: 2469776
• Journal Information: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 2 Vol. 19; ISSN 1932-6203
• Publisher: Public Library of Science
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES