Creutzfeldt-Jakob disease (CJD) is a neurodegenerative condition that is caused by misfolded protein particles (prions). Prion diseases are very rare overall. CJD is the most common prion disease in humans. In most cases, no direct cause of CJD can be established. However, there are also familial forms due to gene mutation or acquired forms as prion particles can be transmitted between individuals, making CJD an infectious disease. Accumulation of prion particles in the brain eventually leads to neuronal degeneration and clinical onset of the disease. The cardinal symptoms of CJD are rapidly progressive dementia and myoclonus. Most patients die within 12 months following disease manifestation. Imaging, EEG, and cerebrospinal fluid (CSF) tests provide diagnostic evidence, although a definite diagnosis can only be made via biopsy or autopsy. To date, no curative treatment is available.
- CJD is the most common prion disease in humans. 
- In the US, there are approximately 1–1.5 cases of sporadic CJD per million population annually.
- Mean age of onset of sporadic CJD: ∼ 60 years 
Epidemiological data refers to the US, unless otherwise specified.
- Sporadic: (∼ 85%): no identifiable source
- Familial: (∼ 10–15%): associated with various mutations (e.g., deletions, insertions, nonsense or missense variants) affecting the prion protein gene (PRNP gene) 
Acquired (< 1%)
- Iatrogenic CJD: transmission during medical procedures, such as:
- Variant CJD (vCJD)
- Conversion of normal cellular prion proteins with alpha-helical structure (PrPc) to prions that demonstrate an increase in beta-pleated sheet structure (PrPSc) → conformational change of physiological PrPc; → PrPSc accumulation and plaque formation → neuronal cell death → progression to spongiform encephalopathy 
- Since misfolded prions are insoluble, they deposit as plaques resistant to proteases and standard autoclaving, thus contributing to the formation of more PrPSc.
- Prodromal symptoms
- Neurological symptoms
- Neuropsychiatric symptoms
- Autonomic nervous system dysregulation (e.g., sweating)
Instrumental diagnostics 
- CSF analysis 
RT-QuIC: a diagnostic tool for sporadic Creutzfeldt-Jakob disease 
- Involves mixing of CSF taken from an individual with suspected CJD with recombinant prion protein (rPrP) and thioflavin T.
- If CSF contains PrPSc, PrPSc will induce conformation changes in rPrP.
- Aggregated rPrP fibrils bind to thioflavin T, which will start to fluoresce.
- Fluorescence can be measured and shows a characteristic sigmoidal curve.
- The whole process can take up to 90 hours.
- Imaging: MRI frequently shows hyperintensity in the basal ganglia, insular cortices, and the frontal cortices
- EEG: triphasic periodic sharp wave complexes with a frequency of 1–2 Hz
- Diagnosis can only be confirmed by biopsy/autopsy and subsequent neuropathological examination.
- Microscopic findings include spongiform degeneration (e.g., intracytoplasmic vacuoles within the neurons of cerebral and cerebellar cortex that can be seen on H&E), gliosis and, in rare cases, amyloid plaques.
Other diseases commonly associated with the development of dementia:
- Other prion diseases
- Encephalopathy due to mitochondrial myopathy (e.g., )
- Wilson disease
- See “ .”
The differential diagnoses listed here are not exhaustive.