A blood miRNA signature associates with sporadic Creutzfeldt-Jakob disease diagnosis.
Aged
Alzheimer Disease
/ genetics
Biomarkers
/ blood
Cohort Studies
Creutzfeldt-Jakob Syndrome
/ blood
Disease Progression
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Longitudinal Studies
Male
MicroRNAs
/ blood
Middle Aged
RNA, Messenger
/ genetics
ROC Curve
Reproducibility of Results
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 08 2020
07 08 2020
Historique:
received:
31
10
2019
accepted:
09
07
2020
entrez:
10
8
2020
pubmed:
10
8
2020
medline:
10
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32769986
doi: 10.1038/s41467-020-17655-x
pii: 10.1038/s41467-020-17655-x
pmc: PMC7414116
doi:
Substances chimiques
Biomarkers
0
MicroRNAs
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3960Subventions
Organisme : Medical Research Council
ID : MC_U123160657
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U123160651
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400713
Pays : United Kingdom
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