Investigating the pre-mortem diagnostic potential of neurofilament light chain in bovine spongiform encephalopathy

Abstract

Transmissible spongiform encephalopathy is a group of neurodegenerative diseases that affect the central nervous system. They result from the misfolding of a normal cellular prion protein (PrPC) into its abnormal isoform called scrapie prion protein (PrPSc). These groups of diseases affect different species, including chronic wasting disease (CWD) in cervids, scrapie in sheep and goats, Creutzfeldt-Jakob disease (CJD) in humans, and bovine spongiform encephalopathy (BSE) in cattle. BSE is particularly concerning because it is zoonotic and may cause variant CJD in humans when BSE-contaminated meat is consumed. Diagnosing BSE involves post-mortem testing that requires euthanasia and brain extraction, which is invasive, time-consuming, and expensive. Given these limitations, it is paramount to explore the potential for BSE detection in live cattle, with surrogate biomarkers being the most promising approach. A candidate biomarker that should be easily detectable in live subjects using a less invasive method, such as blood sampling. In this context, neurofilament light (NfL), a protein biomarker, is well documented in the literature and has been successfully identified in both the cerebrospinal fluid (CSF) and blood in cases of scrapie and CJD. Since neuronal loss is a key hallmark of prion diseases, and NfL is a marker of neuronal damage, it can be a favourable candidate biomarker. This study examined the potential of NfL as a premortem diagnostic tool for detecting BSE. This was accomplished by assessing NfL regulation in relation to PrPSc deposition in the brains, followed by analysis of NfL levels in the CSF and blood of both BSE-positive and BSE-negative cattle. Overall, this study is the first to provide evidence of NfL's potential to differentiate between BSE-positive and healthy cattle premortem.