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Cerebrospinal Fluid and Plasma Small Extracellular Vesicles and miRNAs as Biomarkers for Prion Diseases
Óscar López-Pérez1,2,3, David Sanz-Rubio1,4, Adelaida Hernaiz1
1Laboratorio de Genética Bioquímica (LAGENBIO), Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria de Aragón (IISAragón), Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
Abstract:
Diagnosis of transmissible spongiform encephalopathies (TSEs), or prion diseases, is based on the detection of proteinase K (PK)-resistant PrPSc in post-mortem tissues as indication of infection and disease. Since PrPSc detection is not considered a reliable method for in vivo diagnosis in most TSEs, it is of crucial importance to identify an alternative source of biomarkers to provide useful alternatives for current diagnostic methodology. Ovine scrapie is the prototype of TSEs and has been known for a long time. Using this natural model of TSE, we investigated the presence of PrPSc in exosomes derived from plasma and cerebrospinal fluid (CSF) by protein misfolding cyclic amplification (PMCA) and the levels of candidate microRNAs (miRNAs) by quantitative PCR (qPCR). Significant scrapie-associated increase was found for miR-21-5p in plasma-derived but not in CSF-derived exosomes. However, miR-342-3p, miR-146a-5p, miR-128-3p and miR-21-5p displayed higher levels in total CSF from scrapie-infected sheep. The analysis of overexpressed miRNAs in this biofluid, together with plasma exosomal miR-21-5p, could help in scrapie diagnosis once the presence of the disease is suspected. In addition, we found the presence of PrPSc in most CSF-derived exosomes from clinically affected sheep, which may facilitate in vivo diagnosis of prion diseases, at least during the clinical stage.
Insights
Researchers identified potential biomarkers for diagnosing prion diseases like scrapie in sheep. Detecting PrPSc in cerebrospinal fluid exosomes and specific microRNAs in plasma and CSF offers hope for earlier in vivo diagnosis.
Area of Science:
- Neuroscience and Neurology
- Biochemistry and Molecular Biology
- Veterinary Medicine
Background:
- Transmissible spongiform encephalopathies (TSEs), or prion diseases, are diagnosed post-mortem via PrPSc detection.
- Current methods lack reliable in vivo diagnostic capabilities for most TSEs.
- Ovine scrapie serves as a key model for studying TSEs and developing diagnostic tools.
Purpose of the Study:
- To investigate PrPSc presence in exosomes from plasma and cerebrospinal fluid (CSF) of scrapie-infected sheep.
- To quantify levels of candidate microRNAs (miRNAs) in plasma and CSF exosomes.
- To identify potential biomarkers for in vivo diagnosis of ovine scrapie.
Main Methods:
- Protein misfolding cyclic amplification (PMCA) was used to detect proteinase K (PK)-resistant PrPSc.
- Quantitative PCR (qPCR) was employed to measure microRNA (miRNA) levels.
- Exosomes were isolated from plasma and CSF samples of sheep.
Main Results:
- PrPSc was detected in CSF-derived exosomes from clinically affected sheep.
- Plasma-derived exosomes showed a significant increase in miR-21-5p levels in scrapie cases.
- Elevated levels of miR-342-3p, miR-146a-5p, miR-128-3p, and miR-21-5p were observed in total CSF.
Conclusions:
- PrPSc detection in CSF exosomes may aid in vivo diagnosis of prion diseases during clinical stages.
- Specific miRNAs (miR-21-5p in plasma exosomes, and miR-342-3p, miR-146a-5p, miR-128-3p, miR-21-5p in CSF) show diagnostic potential for scrapie.
- Combined analysis of these biomarkers could improve early detection of suspected prion disease cases.
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