Prion disease and the transmission model

Question 1

What are the types of animal prion diseases, and the human ones?

Answer 1

Scrapie (sheep)
Bovine spongiform encephalopathy
Feline spongiform encephalopathy
Chronic wasting disease
Transmissible mink encephalopathy

CJD (sporadic, iatrogenic, familial,variant)
Kuru
Gerstmann-Straussler-Sheinker syndrome.

Question 2

What is the neuropathology of prion diseases?

Answer 2

Spongiform change
Neuronal loss (atrophy)
Astrogliosis
Synaptic loss
Accumulation of PrP.

Question 3

What are the symptoms and clinical characteristics of sporadic CJD, GSS, and fatal insomnia?

SEE TABLE.

Answer 3

CJD:
Progressive dementia
EEG changes
Motor disturbances
Death within a year. 

Fatal insomnia
Sporadic or genetic. Motor symptoms (ataxia), insomnia seizures.

GSS:
Dementia, ataxia, extrapyramidal and pyramidal signs. Genetic.

Question 4

What are the characteristics of normal and pathogenic prion protein?

Answer 4

Normal cellular protein PrPc. Expressed in neurons and glia, chromosome 20. Membrane associated.

Pathogenic protein is PrPp. Folds to PrPSc. Accumulates in cells and amyloid deposits. Resistant to degradation by proteinase K. Detectable by ICC.

Question 5

What are normal functions of PrPc?

Answer 5

Signal transduction
Vesicle trafficking
Anti-apoptotic
ECM interactions
Heat shock protein
Chaperone
Metal binding

Question 6

What are some proposed mechanisms of spread?

Answer 6

Gut lumen: Prion protein taken up by enteric nervous system, transported up to CNS via vagus and splanchnic nerve circuitry.

Cells release aggregate, which is taken up by other cells. This induces conformational changes.

Question 7

What are some therapeutic approaches?

Answer 7

Pentosan polysulphate.

Ablation of FDCs

Vaccination