Prions Flashcards
Definition of prion
infectious protein
Different animals can have prion diseases. In humans, there are 5 recognized ones.
- Kuru
- Fatal Familial Insomnia
- Gerstmann-Stassler-Scheinker syndrome
- variant Cretzfeldt-Jacob Disease (vCJD)
- Creutzfeldt-Jacob Disease (CJD)
CJD is the most common prion disease in humans. What are some causes?
- sporadic (sCJD) -no known cause accounting for 85-95%)
- familial (fCJD) -inherited risk (7-10%)
- iatrogenic (iCJD) -exposure during medical procedures (<1%)
Is sCID related to human “mad cow disease”
No, it is not what we know today as mad cow disease
T/F: sCJD can be transmitted person-to-person by blood transfusion or meat contaminated with BSE.
False
Symptoms of sCJD
- spongiform encephalopathy
- loss of brain function resembles Alzheimers, but occurs RAPIDLY
- complete dementia usu. occurs by the 6th month
- death occurs within one year of symptom onset
What are the two cardinal symptoms and signs of sCJD?
1) mental deterioration -delirium, dementia, mood changes
2) myoclonus -muscle twitching, provoked by startle
What causes prion diseases?
Protein-only hypothesis (not caused by microbes b/c lack of immune response)
Prions are encoded by the host by which gene?
PrPc gene (cellular form) is involved in maintaining brain’s white matter, neuron formation.
Protein misfolding converts PrPc to
PrPsc (scrapie form) -beta sheet
T/F: PrPsc can be experimentally transmitted to animals
True
There are 4 types of PrPsc. How can you tell them apart?
Different results when in proteinase K
- Type 1 is associated with sCJD
- Type 4 is associated with vCJD
How to diagnose prion diseases?
-Brain biopsy using hematoxylin and eosin stain of thin brain section
How to characterize sCJD in biopsy?
1) spongiform change
2) neuronal loss w/o inflammation
3) accumulation of PrPsc
Electroencephalography (EEG) and MRI are normal or abnormal in someone with sCJD?
Abnormal
T/F: sCJD was higher among children.
False; sCJD is higher among the older population
Does sCJD seem to affect one racial group over another?
yes, whites
vCJD is associated with BSE (mad cow disease). What type of prion is it?
Type 4 prion
vCJD is transmitted bovine-to-human transmission. If muscle and milk are contaminated with BSE, can one get vCJD?
Yes
Brain deteriorates faster or slower in vCJD than in sCJD?
Slower in vCJD, but still rapid in comparison to Alzheimer’s. (12 months for vCJD vs 4-5 months for sCJD)
Major difference between vCJD and sCJD is
vCJD has a peripheral pathogenesis with prominent involvement of lymphoreticular tissues (tonsils, spleen)
Will patient with vCJD have abnormal or normal EEG and MRI?
Abnormal
Absolute method to differentiate btw vCJD and sCJD?
Brain biospy
-vCJD will have brown amyloid cores surrounded by vacuoles which are absent in sCJD
T/F: vCJD affects a lot younger people than sCJD
Yes, avg age of people affected by vCJD is around 29 compared to 60ish in sCJD.
vCJD epidemic peaked between
1999-2000 (about 8 yrs after the BSE epidemic)
Since 1996, CDC has only received how many confirmed patients of vCJD?
3 patients
Why do we need to be aware of vCJD?
About 1 in 2000 people in UK carry the vCJD-causing prion. The incubation period might be 20-30 years. May be a problem in the future.
T/F: Prions are highly resistant to disinfectants, heat, UV radiation, ionizing radiation, and formalin.
True
