Serum neurofilament light chain concentrations in sheep inoculated with classical scrapie: a time point study

dc.contributor.advisor Greenlee, Heather
dc.contributor.advisor Cassmann, Eric
dc.contributor.advisor Greenlee, Justin
dc.contributor.author Brown, Quazetta Lenae
dc.contributor.department Department of Biomedical Sciences
dc.date.accessioned 2023-08-29T10:18:01Z
dc.date.available 2023-08-29T10:18:01Z
dc.date.issued 2023-08
dc.date.updated 2023-08-29T10:18:01Z
dc.description.abstract Neurofilament light chain (Nf-L) is a structural protein of neurons. When a neuron is damaged, Nf-L is released in the cerebral spinal fluid and blood. Generally, rises in Nf-L in blood serum are indicative of neuronal damage, which make it a non-specific biomarker for neurologic 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. Four sheep with the prion protein genotype AVQQ were intranasally inoculated with classical scrapie strain x124. Blood was spun and serum was collected. Serum was processed on a Quanterix SR-X platform to evaluate Nf-L concentrations at each timepoint and at the time of euthanasia. 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, PrPSc accumulation was not detected antemortem by immunohistochemistry (IHC) in rectal tissue at any timepoint for any sheep. Real-Time Quaking-Induced Conversion (RT-QuIC) results were inconsistently positive throughout the timepoints tested for each sheep. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, rise in levels 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.
dc.format.mimetype PDF
dc.identifier.doi https://doi.org/10.31274/td-20240329-670
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/Ewpa3Jbv
dc.language.iso en
dc.language.rfc3066 en
dc.subject.disciplines Neurosciences en_US
dc.subject.keywords Neurofilament Light en_US
dc.subject.keywords prion en_US
dc.subject.keywords SiMoA en_US
dc.title Serum neurofilament light chain concentrations in sheep inoculated with classical scrapie: a time point study
dc.type thesis en_US
dc.type.genre thesis en_US
dspace.entity.type Publication
relation.isOrgUnitOfPublication 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9
thesis.degree.discipline Neurosciences en_US
thesis.degree.grantor Iowa State University en_US
thesis.degree.level thesis $
thesis.degree.name Master of Science en_US
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