scary prions Flashcards
what PrPsc types have been seen in the classical forms of CJD?
1-3
how do prions “replicate”
once PrPsc is formed, the nucleus (“seed”) recruits other PrPc and converts them to PrPsc.
from there, nucleus increases in size to become an amyloid fiber
fragmentation then occurs
how do you test for CJD?
brain biopsy is golden standard
what types of medical tests will be abnormal in a person with CJD?
MRI
EKG
what is the brain biopsy of a person with sCJD characterized by?
accumulation of PrPsc
neuronal loss without inflammation
spongiform change
in sCJD, what is the average disease duration? when does death usually occur?
disease duration is 5-6 months
death usually occurs within 1 year of symptom onset
what age group does sCJD seem to present in?
older population
median age is 68
what prion type causes vCJD?
type 4
compare the disease progression of vCJD, sCJD and Alzheimer’s
alzherimer disease progression is much slower than the two types of CJD. sCJD has the FASTEST disease progression
what is the illness duration of vCJD?
14 months
what tissues have prominent involvement in vCJD that is not seen in sCJD (or iCJD)?
prominent involvement of lymphoreticular tissues
vCDJ has special tropism for lymphoid tissues
list some differences between sCJD and vCJD that can allow for differentiation?
type of PrPsc
MRI signal is different from one another
in patients with sCJD there is abnormal PrP deposition
in cCJD florid PrP plaques consist of a round amyloid core surrounded by spongiform VACUOLES!
mean age of onset for vCJD?
29 years
how is vCJD transmitted?
person-person through blood transfusion or ingestion of food contaminated with BSE
what is the average incubation period for vCJD?
20-30 years!
list new targets for CJD treatment
- PrP13: breaks the beta sheet confirmation and has been shown to delay symptoms
- anti-PrP monoclonal antibodies
- adenovirus vector platforms that express PrPc single chain fragment
what two animals is the disease scarpie seen in?
sheep and goat
what two animals is chronic wasting disease disease?
deer and elk
list the 5 prion diseases seen in humans
kuru fatal familial insomnia (FFI) GSS syndrome vCJD sCJD
what is the cause of sCJD and what percentage of CJD does it make up?
no known cause 85-95%
what is the cause of fCJD and what percentage of CJD does it make up?
inherited genetic risk 7-10%
what is the cause of iCJD and what percentage of CJD does it make up?
exposure during medical procedures <1%
what are the 2 cardinal clinical manifestations of sCJD?
metal deterioration and myoclonus
what gene encodes for the prion protein?
Prnp gene
what is the structure of PrPc?
alpha helix
what is the structure of PrPsc?
beta sheet
what are the proposed functions of PrPc?
maintain white matter, regulate innate immune cells, respond to oxidative stress and neuron formation
how were the 4 types of CJD found?
by observing different fragment sizes observed in western blots following treatment with proteinase K
Can sCJD be transported between person to person (blood transfusions)? What about eating BSE contaminated meat?
NO
What is myoclonus? Who is it seen in ?
It is an un-voluntary muscle jerk
Seen in patients with sCJD
List 3 things that have led to the protein only hypothesis
No nucleus Acids
Agent is resisted to UV radiation and nuclear es
No immune response to infection
List 3 reasons why Alzheimer’s is thought to be linked to prions
- Polymorphism in prp gene is a risk Factor for AD
- PrPc binds to amyloid B peptides
- Mice injected with brain tissue from AD patient will develop disease
