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

Abstract Prion diseases are distinguished by long pre-clinical incubation periods during which prions actively propagate in the brain and cause neurodegeneration. In stage, we hypothesize that upon prion infection, transcriptional changes occur can lead to early A longitudinal analysis of miRNAs clinical forms murine disease demonstrated dynamic expression progression affected thalamus region serum. Serum samples at each timepoint were collected whereby extracellular vesicles (EVs) isolated used identify blood-based biomarkers reflective pathology brain. Differentially expressed EV validated human from patients with sporadic Creutzfeldt-Jakob (sCJD), molecular subtype codon 129 either methionine-methionine (MM, n = 14) or valine-valine (VV, 12) compared controls ( 20). miRNA associated infection predicted sCJD an AUC 0.800 (85% sensitivity 66.7% specificity) a second independent validation cohort 26) control MM VV subtype. This study discovered clinically relevant benefit diagnostic development detect prion-related therapeutic inhibit infectivity.