Distribution of microRNA profiles in pre-clinical and clinical forms of murine and human prion disease

Cheng, Lesley ORCID: 0000-0002-8075-6144, Quek, Camelia ORCID: 0000-0002-1244-961X, Li, Xia, Bellingham, Shayne A ORCID: 0000-0001-5657-7413, Ellett, Laura, Shambrook, Mitch, Zafar, Saima, Zerr, Inga, Lawson, Victoria A ORCID: 0000-0002-7362-7176 and Hill, Andrew F ORCID: 0000-0001-5581-2354 (2021) Distribution of microRNA profiles in pre-clinical and clinical forms of murine and human prion disease. Communications Biology, 4 (1). ISSN 2399-3642


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.

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Item type Article
URI https://vuir.vu.edu.au/id/eprint/45737
DOI 10.1038/s42003-021-01868-x
Official URL https://www.nature.com/articles/s42003-021-01868-x
Subjects Current > FOR (2020) Classification > 3105 Genetics
Current > FOR (2020) Classification > 3209 Neurosciences
Current > Division/Research > Chancellery
Keywords prion disease, diseases, neurodegeneration, prion protein, PrP
Citations in Scopus 7 - View on Scopus
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