Prion Disease - A. Prunuske

Question 1

What are the etiologies of prion disease?

Answer 1

• acquired through cannibalism (infectious)
  
  • Kuru
• consumption of meat contaminated with Bovine Spongiform Encephalopathy (infectious)
  
  • Creutzfeldt-Jakob Disease
• hormones from cadaver pituitaries (environmental)
  
  • Iatrogenic
• contamination of grafts or surgical instruments (infectious)
  
  • Iatrogenic
• corneal transplants
  
  • Iatrogenic
• large number of mutations in PRNP gene with different disease phenotypes (genetic)
  
  • Familial Creutzfeldt-Jakob Disease
• sporadic, etiology unknown, no known risk factors

Question 2

What is the basic mechanism of prion diseases?

Answer 2

• Infectious agent is the PrP protein, which can exist in two major forms:
  
  • PrP^C = Normal protein
  • PrP^SC = Misfolded protein
  • there are different strains that vary in their infectivity
• The Prp^SC converts PrP^C forming an amyloid

Question 3

What is the pathology of prion disease?

Answer 3

• The PrpSC converts PrPC forming an amyloid
  
  • amyloid = fibrous protein deposits, often associated with disease
  • amyloids initiate unfolded protein response and increased vacuolization

Question 4

What are possible clinical/laboratory/procedural/imaging tests that can be used to identify prion disease?

Answer 4

• No single test to diagnose
  
  • LP = rule out meningitis
  • CT = rule out tumor
  • EEG = periodic, sharp wave complexes
    
    • disease can be spread this way
  • MRI = high intensity - putament/caudate nucleus (“hockey stick”) or pulvinar thalamic nucleus
  • CSF = elevation of protein 14-3-3 marker of neuronal degeneration
  • Biochemistry = Western blotting of PrP^SC following proteinase digestion
  • DNA Sequencing = Mutations of PRNP gene
  • Brain Biopsy = look for characteristic spongy change

Question 5

What is the risk of contracting prion disease after exposure to deer with Chronic Wasting Disease?

Answer 5

• Horizontal transmission of chronic wasting disease occurs readily between cervids (deer)
• Prion can be found in urine, feces, saliva, and ground water
  
  • Can cross BBB
• Intracerebral innoculation of CWD
  
  • ​squirrel monkeys –> got CWD
  • cynomulgas macaques (monkey) –> did not get CWD
  • humans are evolutionarily closer to macaques, suggesting humans may also be resistance to CWD
• ​5 cases of CWD from 1997-2000
  
  • ​26-30 yo male hunters

Question 6

Compare and contrast prion disease to Alzheimer Disease.

Answer 6

• Alzheimer Disease
  
  • Amyloid beta peptide aggregates
  • Neurofibrillary tangles
  • not infectious
  • slow, gradual onset
  • Acetylocholine
  • neurological deficits
  • fatal
• Prion disease
  
  • Amyloid prion protein aggregates
  • vacuolization
  • infectious
  • rapid onset, rapid progression
  • epidemiology pattern
  • neurological deficits
  • fatal