11th August 2024

Human prion disease – Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a rare and inevitably fatal cause of progressive dementia with neurological symptoms. Intracellular human prion proteins are misfolded from an alpha-helical structure into a beta-pleated form, which in turn causes adjacent proteins to undergo this transformation. These ‘infectious proteins’ drive the pathophysiology of neuronal injury and eventual cell death as a result of accumulation of abnormal prion proteins in the CNS.

There are three main types of CJD:

• Sporadic (sCJD) – accounts for the majority of cases, up to 90% of CJD
• Acquired – include iatrogenic CJD (iCJD) (transmission of prion protein from contaminated surgical equipment or cadaveric tissue grafts) and variant CJD (vCJD) (ingestion of CJD-contaminated beef or blood transfusion)
• Familial – mutations in the gene coding for PRNP (endogenous prion protein) on chromosome 20; usually autosomal dominant with 100% penetrance, however, clinical presentation can be variable and less aggressive than sCJD and vCJD

Diagnosis of CJD

CSF examination – can be bland with mildly raised protein. Elevated 14-3-3 protein has high sensitivity and specificity for sCJD but is not useful for vCJD; real-time quaking-induced conversion for abnormal prions has high sensitivity and specificity.

EEG – periodic triphasic spikes

Imaging – MRI brain with FLAIR (fluid attenuated inversion recovery) and diffusion-weighted imaging (DWI) best demonstrates affected areas:

• sCJD – hyperintensities in the basal ganglia (caudate and putamen) and ‘cortical ribboning’ on DWI
• vCJD – bilateral periventricular thalamic hyperintensities, ‘hockey stick sign’

Image Source: ncbi.nlm.nih.gov 2025, PMC5619326, Licensed under a creative commons licence. Available for free at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619326/pdf/dn-09-04-0424.pdf  (Accessed: 17 July 2024)

Image Source: ncbi.nlm.nih.gov 2025, PMC5619326, Licensed under a creative commons licence. Available for free at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619326/pdf/dn-09-04-0424.pdf  (Accessed: 17 July 2024)