Unclear etiology of sporadic Creutzfeldt-Jakob disease

Determine the etiology of sporadic Creutzfeldt-Jakob disease (sCJD) in humans.

Background

The paper reviews the clinical presentation, diagnostic workup, and classification of sporadic Creutzfeldt-Jakob disease (sCJD), noting established diagnostic biomarkers and imaging patterns such as CSF 14-3-3, elevated tau, and DWI cortical ribboning. Despite these advances in diagnosis, the underlying cause of sporadic onset remains unresolved.

The authors highlight possible mechanisms discussed in the literature, including PRNP mutations and spontaneous misfolding of cellular prion protein (PrPC) into the pathogenic isoform, but explicitly state that the etiology of sCJD is not clear, underscoring a fundamental open question in the field.