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Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie

Betancor, M; Pérez-Lázaro, S; Otero, A; Marín, B; Martín-Burriel, I; Blennow, K; Badiola, JJ; ... Bolea, R; + view all (2022) Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie. International Journal of Molecular Sciences , 23 (13) , Article 7182. 10.3390/ijms23137182. Green open access

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Abstract

Prion diseases are diagnosed in the symptomatic stage, when the neuronal damage is spread throughout the central nervous system (CNS). The assessment of biological features that allow the detection of asymptomatic cases is needed, and, in this context, scrapie, where pre-symptomatic infected animals can be detected through rectal biopsy, becomes a good study model. Neurogranin (Ng) and neurofilament light chain (NfL) are proteins that reflect synaptic and axonal damage and have been studied as cerebrospinal fluid (CSF) biomarkers in different neurodegenerative disorders. In this study, we evaluated Ng and NfL both at the protein and transcript levels in the CNS of preclinical and clinical scrapie-affected sheep compared with healthy controls and assessed their levels in ovine CSF. The correlation between these proteins and the main neuropathological events in prion diseases, PrPSc deposition and spongiosis, was also assessed. The results show a decrease in Ng and NfL at the protein and gene expression levels as the disease progresses, and significant changes between the control and preclinical animals. On the contrary, the CSF levels of NfL increased throughout the progression of the disease. Negative correlations between neuropathological markers of prion disease and the concentration of the studied proteins were also found. Although further research is needed, these results suggest that Ng and NfL could act as biomarkers for neurodegeneration onset and intensity in preclinical cases of scrapie.

Type: Article
Title: Neurogranin and Neurofilament Light Chain as Preclinical Biomarkers in Scrapie
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms23137182
Publisher version: https://doi.org/10.3390/ijms23137182
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Keywords: prion; prion diseases; scrapie; biomarkers; neurodegeneration; neurogranin; neurofilament light chain
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/10152482
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