Sporadic Creutzfeldt–Jakob disease (sCJD) is the most common human prion disorder and accounts for about 85 % of all Creutzfeldt–Jakob disease cases. It arises without a known source of infection or inherited mutation and is thought to result from the spontaneous misfolding of the cellular prion protein (PrP^C) into the pathogenic isoform (PrP^Sc). Misfolded PrP seeds the conversion of normal prion protein and accumulates in the brain, leading to neuronal loss, spongiform degeneration and astrocytic gliosis. sCJD usually occurs in adults aged 55–75 years and progresses rapidly.
Pathogenesis, Subtypes and Diagnosis
Prions are infectious proteins that lack nucleic acid. In sCJD the initial trigger for conversion of PrP^C to PrP^Sc is unknown, but different conformations of PrP^Sc and host PRNP codon 129 genotypes give rise to molecular subtypes (e.g., MM1, MV2, VV1). These subtypes correlate with variations in clinical presentation, neuropathology and disease course. The disease is characterised by rapidly progressive cognitive decline, behavioural changes, myoclonus, ataxia and visual disturbances. Median survival is around six months from symptom onset. Laboratory diagnosis is supported by characteristic changes on magnetic resonance imaging (cortical ribboning and basal ganglia hyperintensity), periodic sharp wave complexes on electroencephalogram, detection of 14‑3‑3 protein or elevated tau in cerebrospinal fluid and the highly specific real‑time quaking‑induced conversion (RT‑QuIC) assay. A brain biopsy or autopsy remains the definitive diagnostic method. There is no curative therapy; care is supportive.
Incidence and Public Health Considerations
sCJD has a worldwide incidence of approximately one to two cases per million people per year. It is not considered contagious under ordinary circumstances because transmission requires exposure to infected central nervous system tissue. However, prion infectivity resists conventional sterilisation, and iatrogenic transmission has occurred via contaminated neurosurgical instruments, corneal transplants and human‑derived pituitary hormones. Consequently, strict infection control protocols, including the disposal or specialised decontamination of instruments exposed to high‑risk tissues, are essential. Surveillance programmes in many countries monitor CJD cases to detect unusual patterns that might signal new infectious sources, such as the emergence of variant CJD associated with bovine spongiform encephalopathy. sCJD exemplifies how a change in protein conformation can underlie a fatal neurodegenerative disease. Ongoing research aims to unravel the mechanisms initiating prion misfolding and to develop diagnostic and therapeutic strategies that can alter the course of this rapidly progressive dementia. Related Terms: Familial Creutzfeldt–Jakob Disease, Iatrogenic Creutzfeldt–Jakob Disease, Variant Creutzfeldt–Jakob Disease, Gerstmann–Sträussler–Scheinker Syndrome, Kuru