Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt–Jakob disease

16Citations
Citations of this article
39Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Prion diseases are fatal and transmissible neurodegenerative disorders caused by the misfolding and aggregation of prion protein. Although recent studies have implicated epigenetic variation in common neurodegenerative disorders, no study has yet explored their role in human prion diseases. Here we profiled genome-wide blood DNA methylation in the most common human prion disease, sporadic Creutzfeldt–Jakob disease (sCJD). Our case–control study (n = 219), when accounting for differences in cell type composition between individuals, identified 38 probes at genome-wide significance (p < 1.24 × 10–7). Nine of these sites were taken forward in a replication study, performed in an independent case–control (n = 186) cohort using pyrosequencing. Sites in or close to FKBP5, AIM2 (2 probes), UHRF1, KCNAB2 successfully replicated. The blood-based DNA methylation signal was tissue- and disease-specific, in that the replicated probe signals were unchanged in case–control studies using sCJD frontal-cortex (n = 84), blood samples from patients with Alzheimer’s disease, and from inherited and acquired prion diseases. Machine learning algorithms using blood DNA methylation array profiles accurately distinguished sCJD patients and controls. Finally, we identified sites whose methylation levels associated with prolonged survival in sCJD patients. Altogether, this study has identified a peripheral DNA methylation signature of sCJD with a variety of potential biomarker applications.

Cite

CITATION STYLE

APA

Dabin, L. C., Guntoro, F., Campbell, T., Bélicard, T., Smith, A. R., Smith, R. G., … Viré, E. (2020). Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt–Jakob disease. Acta Neuropathologica, 140(6), 863–879. https://doi.org/10.1007/s00401-020-02224-9

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free