Prion diseases

Question 1

Prion diseases

Answer 1

Transmissible and neurodegenerative
Prolonged incubation period 
Sporadic (no obvious cause)
Acquired (infectious agent)
Inherited (mutations in prion protein)

Question 2

Scrapie

Answer 2

Common in sheep
Itching sensation leads to scratching and loss of wool
Locomotor disturbance, tremors and aggression

Question 3

BSE

Answer 3

Bovine spongiform encephalopathy
Affects cattle
Possibly fed meat contaminated with sheep scrapie
Infectious agent remains viable at high temperatures

Question 4

Kuru

Answer 4

Epidemic affecting tribe in Papua New Guinea due to cannibalism
Mean incubation period of 12 years

Question 5

CJD

Answer 5

Creutzfeldt-Jakob disease
No person to person transmission
Transmission by surgical procedures
Transmitted to humans as new variant CJD (vCJD)

Question 6

CJD symptoms

Answer 6

Loss of balance and co-ordination
Slurred speech
Vision problems and blindness
Loss of mobility
Most die within a year of symptoms appearing

Question 7

Neuropathological changes in prion disease

Answer 7

Vacuolation (spongiform changes) in grey matter and spinal cord
PrP-positive amyloid plaques and scrapie-associated fibrils (SAF)
Astrocyte proliferation
Neuron and synapse depletion

Question 8

Scrapie agent identification

Answer 8

Initially thought to be slow virus
Resistant to radiation, nuclease digestion, heat and chemicals
Can replicate without nucleic acid
Identified as Proteinaceous infectious particle (prion)

Question 9

PrP

Answer 9

PrPc is normal non-infectious cell-surface glycoprotein
Secondary structure dominated by alpha-helices
Soluble and digested by proteases
Role unknown

Question 10

PrPsc

Answer 10

Scrapie form (same AA sequence)
Infectious
Secondary structure dominated by beta-helices
Insoluble and highly resistant to proteases
Converts PrPc to PrPsc
Forms aggregates

Question 11

PrP gene

Answer 11

PRNP
Located on chromosome 20
Mutations make PrPc more susceptible to transformation
Causes familial CJD and fatal familial insomnia
M/V129 increases susceptibility and age of onset

Question 12

Acquired prion disease

Answer 12

Rare form
vCJD only form of human prion disease that has spread from animals to humans
Contaminated beef
Younger age of onset

Question 13

Cause of sporadic prion disease

Answer 13

Somatic mutation in PrP ORF
RNA editing error
Protein translational error
Mistake in protein folding (may involve chaperones)