Year 1 Prions

Question 1

Definition/concept

Answer 1

accumulation of diseased prions in nervous tissue leads to prion disease of transmissible spongiform encephalopathy (TSE)

Question 2

Examples of prion disease in humans (3)

Answer 2

1. Creutzfeldt Jacob Disease (CJD) - mad cow
2. Gerstmann-Straussler-Scheinker syndrome (GSSS)
3. Fatal familial insomnia (FFI)

Question 3

Key points: (4)

Answer 3

• Always fatal
• Neurodegenerative
• No known effective treatment
• Mechanism of pathogenesis is poorly understood

Question 4

Scrapie:
History?
Symptoms?

Answer 4

18th century, sheep and goats, 2-5 year incubation period.
1930’s transmissibility demonstrated

Symptoms:
scratching, tremors and change in behaviour

Question 5

Kuru:
History?
Clinical Presentation

Answer 5

1950s - Papua New Guinea natives (cannibalism)

Presentation:
more common in men and women 
Emotional changes 
12 month - death 
up to 50 year incubation

Question 6

CJD:
History?
Clinical Presentation

Answer 6

human prion related disease (pre BSE - 1920s)

Numerous types:

• Sporadic - most common
• Iatrogenic - transfer in medical treatment
• Genetic

Question 7

What is BSE?

What is vCJD?

Risk factors of vCJD?

Inactivation? Treatment?

Answer 7

Bovine Spongiform Encephalopathy - 80-90s

• changes in temperament (aggression, anxious)
• posture
• decreased milk
• weight loss
• 2-8 year incubation

vCJD (mad cow disease) - variant in the 90s, caused 10 deaths in young adults

Risk factors:
consumption of contaminated food 
UK resident
Young
Methionine homozygosity at codon 129 (genetic) 

Inactivation: 
Resistant to extreme temp + radiation
NaOH, Sodium hypochlorite 
No effective treatment 
Some experimental drug

Question 8

‘protein-only’ hypothesis?

Answer 8

Infectious agent (prion) is a misfolded isoform of a host cell glycoprotein - an anomaly

Infectious, tendency to aggregate, self-catalyses

Question 9

Possible prion entry sites?

Answer 9

Airways, ingestion, intracranial, skin, IM, IV