Prions Flashcards
1
Q
prion diseases
A
animals-scrapie, feline, chronic wasting in deer and elk, BSE
-humans-5 recognized- kuru, familial insomnia, GSS cCJD CJD
2
Q
CJD
A
- most frequent of human prion diseases
- sporadic-85-95%
- familial- 7-10%
- iatrogenic-<1%
- sCJD cannot be transmitted person to person by blood transfusion or meat contained with BSE
3
Q
sCJD symptoms and signs
A
- sCJD causes spongiform encephalopathy
- loss of brain function resembles AD, but very rapid
- complete dementia usually occurs by the 6th month
- death occurs within one year of symptom onset
- mental deterioration-dementia, concentration, mood changes, sleep probs, impaired speech
- myoclonus (present in >90% at some point)
4
Q
what causes prion disease?
A
- no virus, bacteria, fungi
- no nucleic acid, resistant to UV and nucleases
- no immune response
- protein only hypothesis
5
Q
against protein hypothesis
A
- AD, parkinsons, huntingtons are characterized by misfolded proteins-not infectious-misfolded protein not enough…? AD infectious?
- spongiform diseases come in distinct strains that differ in their incubation period, symptoms, and effects on brain-due to mutations in nucleic acid, long time incubation and rapid onset resembles HIV
6
Q
PrPc misfolding
A
- prions encoded by host
- Prnp gene encodes a 35kDa membrane glycoprotein in mammals
- PrPc is involved in maintaining the brains white matter, regulating innate immune cells, responses to oxidative stress and neuron formation
- protein misfolding converts PrPc to PrPsc leading to prion disease
- PrPsc can arise by mutation or from exogenous sources
- can be experimentally transmitted between animals
- animals lacking PrPc do not contract disease
- PrPsc pathogenesis unknown
7
Q
PrPsc classificatoin
A
- several human types have been identified in brains that are associated with different phenotypes
- different fragment sizes are observed on western blots following treatment with proteinase K
- based on the ratio of the 3 PrP bands seen after digestion, there are 4 types
- 1 and 4 are what we are interested in
8
Q
model for prion self replication
A
- prions are infectious but contain no genetic material
- once formed, nucleus recruits other PrPc and converts them
- nucleus increases in size to become amyloid
- fragmentation occurs-liberates new ends for amp, allows dissemination of infectious material
9
Q
sCJD diagnosis
A
- brain biopsy is gold standard
- spongiform change, neuronal loss without IF, accumulation of PrPsc
- can detect protein in CSF protein 14-3-3
- MRI (T2 weighted), EEG (PSWC)
10
Q
sCJD treatment and prognosis
A
- no effective treatment
- median disease duration 5-6 mo
- death with 1 year of symptom onset
11
Q
sCJD epidemiology
A
- from 1979-2006, 6917 deaths
- 247 annually
- annual incidence is 1/1,000,000
- higher among older pop- >65 is 4.8 per mil
- less than 44 is .9 per mil
- median age of death 68, 60-79. white female
12
Q
vCJD
A
- type 4 prion
- bovine to human transmission
- BSE transmitted in cattle via CNA, retina, trigem and paraspinal ganglia, distal ileum and bone marrow
- not milk and muscle
13
Q
vCJD signs and symptoms
A
- similar to sCJD
- loss of brain function slightly slower-14 mo vs 4-5 mo
- peripheral pathogenesis distinct from classical CJD, prominent involvement of lymphoreticular tissues
- fatal
14
Q
vCJD diagnosis
A
- similar to sCJD
- type 4 protein is not in other diseases
- tropism for lymphoid organs like tonsils
- detection for 14-3-3 protein in CSF not sensitive for vCJD
- abnormal MRI and EEG (slow wave)
- plaques with round amyloid core surrounded by spongiform vacuoles instead of diffuse staining
15
Q
mean age of vCJD
A
29 (11-79)
