Prion Disease


Prion Disease, Transmissible Spongiform Encephalopathy, Prion Protein Disease, Prion, Prion Protein, PrP Protein, Mad Cow Disease, Scrapie, Bovine Spongiform Encephalopathy, Fatal Familial Insomnia, Gerstmann-Straussler-Scheinker Disease, Kuru

  • Epidemiology
  1. Worldwide: 1 to 1.5 cases per 1 Million per year
  2. U.S.: 1 to 1.2 cases per 1 Million per year (400/year)
  • Definitions
  1. Prion Protein (PrP Protein)
    1. Prion related-Proteins (PrP) are normal components of the cell
    2. Neurodegenerative disorders may occur when these normal PrP are converted to misfolded abnormal prions
    3. Prions are small infectious Protein particles that are resistant to standard forms of inactivation
  2. Prion Disease
    1. Genetic, infectious and sporadic neuro-degenerative disorders (e.g. Dementia, Ataxia) associated with Prion Proteins
  • Causes
  • Humans
  1. Sporadic (>80% of U.S. cases, all Sporadic CJD)
    1. Sporadic Creutzfeldt-Jakob Disease
  2. Genetic (mutations in prion-related Protein gene or PRNP, 10-15% of U.S. cases)
    1. Genetic Creutzfeldt-Jakob Disease
    2. Gerstmann-Straussler-Scheinker Syndrome
      1. Slowly progressive Ataxia or Parkinsonism-like motor disorder with late onset Ataxia
      2. At least 12 mutations have been identified
      3. Onset at median age 50-60 years, but very young age onset may occur (typical range age 20 to 70)
      4. Testing including MRI, EEG and CSF biomarkers are typically non-diagnostic
    3. Fatal Familial Insomnia
      1. Very rare PRNP mutation D178N (cis codon 129M)
      2. Progressive Insomnia over months, autonomic instability (Tachycardia, Hyperhidrosis, fever)
      3. Dementia and motor deficits occur later in course
      4. Typical onset in late 40s and mean survival 18 months
  3. Acquired (rare, <1% of U.S. CJD cases)
    1. Variant Creutzfeldt-Jakob Disease
    2. Iatrogenic Creutzfeldt-Jakob Disease
    3. Kuru (limited to New Guinea tribe cannabils)
  • Causes
  • Animals
  1. Cow CJD (Bovine Spongiform Encephalopathy, Mad Cow Disease)
    1. Transmitted to cows by eating contaminated feed (cattle fed sheep brain)
    2. Transmission from animals to humans (typically Bovine Spongiform Encephalopathy or BSE)
      1. Peak in UK BSE cases (1988-2005) followed by tens of thousands of UK cases (1994-2009)
      2. Since 2012, vCJD cases have been rare
  2. Sheep CJD (Scrapie)
    1. Only transmitted to humans if passed via cattle
  3. Chronic Wasting Disease (CWD, deer and elk)
    1. Possible transmission to humans from exposure to neurologic tissue (butchering) or contaminated meat ingestion
  • Pathophysiology
  1. Transmitted via Prion Protein infectious agents
    1. Prions are the only infectious agent to contain no Nucleic Acids
  2. Prions cause other Proteins to precipitate
    1. Plaques of Prion Proteins form in brain
    2. Results in Spongiform encephalopathy
  3. Prions are very difficult to control
    1. Resistant to disinfectants and sterilization
    2. Environmental decay is very slow
      1. Persists in environment despite removing animals
  4. Transmission
    1. At least 80% of CJD cases are sporadic
    2. Humans may acquire CJD via surgical procedures, transfusions, and contaminated meats (esp. neuro tissue exposure)
      1. Prions travel via lymph
      2. Spreads to brain via Lymphocytes
      3. Disease may have a long latent period after exposure (from 2 to 40 years)
      4. However, once the onset of clinical disease, progression is typically rapid, and uniformly fatal
    3. Animals may spread some Prion Diseases to one another via Saliva (e.g. Scrapie)
      1. Maddison (2010) J Infect Dis 201(11):1672-6 +PMID:20402590 [PubMed]
      2. However this does not appear to be a factor in transmission of Creutzfeldt-Jakob Disease between humans