A blood miRNA signature associates with sporadic Creutzfeldt-Jakob disease diagnosis

• Published in: Nature communications 2020-08, Vol.11 (1), p.3960-3960, Article 3960
• Main Authors: Norsworthy, Penny J., Thompson, Andrew G. B., Mok, Tze H., Guntoro, Fernando, Dabin, Luke C., Nihat, Akin, Paterson, Ross W., Schott, Jonathan M., Collinge, John, Mead, Simon, Viré, Emmanuelle A.
• Format: Article
• Language: English
• Subjects: 38; 38/39; 38/90; 45/77; 45/91; 631/337; 692/617; Aged; Alzheimer Disease - genetics; Alzheimer's disease; Biomarkers - blood; Blood; Blood tests; Bovine spongiform encephalopathy; Cohort Studies; Correlation analysis; Creutzfeldt-Jakob disease; Creutzfeldt-Jakob Syndrome - blood; Creutzfeldt-Jakob Syndrome - diagnosis; Creutzfeldt-Jakob Syndrome - genetics; Creutzfeldt-Jakob Syndrome - pathology; Dementia; Dementia disorders; Diagnosis; Differential diagnosis; Disease control; Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation; Humanities and Social Sciences; Humans; Longitudinal Studies; Male; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; mRNA; multidisciplinary; Neurodegenerative diseases; Phenotypes; Reproducibility of Results; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; ROC Curve; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17655-x

Sporadic Creutzfeldt-Jakob disease (sCJD) presents as a rapidly progressive dementia which is usually fatal within six months. No clinical blood tests are available for diagnosis or disease monitoring. Here, we profile blood microRNA (miRNA) expression in sCJD. Sequencing of 57 sCJD patients, and healthy controls reveals differential expression of hsa-let-7i-5p, hsa-miR-16-5p, hsa-miR-93-5p and hsa-miR-106b-3p. Downregulation of hsa-let-7i-5p, hsa-miR-16-5p and hsa-miR-93-5p replicates in an independent cohort using quantitative PCR, with concomitant upregulation of four mRNA targets. Absence of correlation in cross-sectional analysis with clinical phenotypes parallels the lack of association between rate of decline in miRNA expression, and rate of disease progression in a longitudinal cohort of samples from 21 patients. Finally, the miRNA signature shows a high level of accuracy in discriminating sCJD from Alzheimer’s disease. These findings highlight molecular alterations in the periphery in sCJD which provide information about differential diagnosis and improve mechanistic understanding of human prion diseases. Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive dementia. No clinical blood tests are available for diagnosis. The authors identified three miRNAs in whole-blood that are downregulated in sCJD patients, and discriminate sCJD from Alzheimer’s disease patients and healthy controls.