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Updated: Nov 11, 2025
Cerebrospinal Fluid MicroRNA Profiling Using Quantitative Real Time PCR
Published on: January 22, 2014
Distribution of microRNA profiles in pre-clinical and clinical forms of murine and human prion disease
Lesley Cheng1,2, Camelia Quek3, Xia Li4
1Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia. l.cheng@latrobe.edu.au.
Abstract:
Prion diseases are distinguished by long pre-clinical incubation periods during which prions actively propagate in the brain and cause neurodegeneration. In the pre-clinical stage, we hypothesize that upon prion infection, transcriptional changes occur that can lead to early neurodegeneration. A longitudinal analysis of miRNAs in pre-clinical and clinical forms of murine prion disease demonstrated dynamic expression changes during disease progression in the affected thalamus region and serum. Serum samples at each timepoint were collected whereby extracellular vesicles (EVs) were isolated and used to identify blood-based biomarkers reflective of pathology in the brain. Differentially expressed EV miRNAs were validated in human clinical samples from patients with human sporadic Creutzfeldt-Jakob disease (sCJD), with the molecular subtype at codon 129 either methionine-methionine (MM, n = 14) or valine-valine (VV, n = 12) compared to controls (n = 20). EV miRNA biomarkers associated with prion infection predicted sCJD with an AUC of 0.800 (85% sensitivity and 66.7% specificity) in a second independent validation cohort (n = 26) of sCJD and control patients with MM or VV subtype. This study discovered clinically relevant miRNAs that benefit diagnostic development to detect prion-related diseases and therapeutic development to inhibit prion infectivity.
Insights
Researchers identified specific microRNAs (miRNAs) in extracellular vesicles (EVs) from blood that can detect prion diseases early. These EV miRNA biomarkers show promise for diagnosing sporadic Creutzfeldt-Jakob disease (sCJD) and developing new therapies.
Area of Science:
- Neuroscience
- Molecular Biology
- Biomarker Discovery
Background:
- Prion diseases feature long pre-clinical phases with active prion propagation and neurodegeneration.
- Transcriptional changes in the pre-clinical stage may initiate early neurodegeneration.
- MicroRNAs (miRNAs) are implicated in disease pathogenesis and can be found in extracellular vesicles (EVs).
Purpose of the Study:
- To investigate dynamic miRNA expression changes during prion disease progression in mice.
- To identify blood-based EV miRNA biomarkers for early detection of prion-related neurodegeneration.
- To validate these biomarkers in human sporadic Creutzfeldt-Jakob disease (sCJD) patients.
Main Methods:
- Longitudinal analysis of miRNAs in pre-clinical and clinical prion disease models in mice.
- Isolation of extracellular vesicles (EVs) from serum for miRNA profiling.
- Validation of differentially expressed EV miRNAs in human sCJD patient samples (MM and VV subtypes) and controls.
Main Results:
- Dynamic miRNA expression changes were observed in the thalamus and serum during murine prion disease progression.
- EV miRNA biomarkers associated with prion infection accurately predicted sCJD in an independent human cohort.
- The identified biomarkers achieved an AUC of 0.800, with 85% sensitivity and 66.7% specificity.
Conclusions:
- Clinically relevant EV miRNAs can serve as blood-based biomarkers for prion disease detection.
- These findings support the development of diagnostic tools for prion diseases like sCJD.
- The discovered miRNAs offer potential targets for therapeutic interventions against prion infectivity.
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