MCM 2-40 Prions Flashcards
most frequently observed form of prion disease in humans.
Creutzfeldt-Jacob Disease which has two types
Variant Creutzfeldt-Jacob Disease (cCJD)
Spontaneous Creutzfeldt-Jacob disease (sCJD)
what is the protein only hypothesis?
The hypothesis positing that prion diseases result from the conformational change of a normal isoform of a prion protein (PrPC) to a protease-resistant, pathogenic form (PrPSC). This conversion rests on an autocatalytic process requiring the presence of pre-existing PrPSC.
sCJD
how common? prevalence? transmission? symptoms? prognosis?
typical age?
treatment?
majority of CJD cases (85-95%)
1/1 million
not transmitted by person-person blood transfusion or contaminated BSE meat
spongiform encephalopathy - similar to alz but much more rapid
- rapid mental deterioration
- myoclonus (jerking) provoked by startling
at month 6th, total dementia. at 12 months, death
4-6 month duration of illenss
65 and up
no treatment
two cardinal clinical manifestations of sCJD
loss in brain function resembles Alzheimer’s disease, but is very rapid in progression; rapidly progressive mental deterioration and myoclonus (spasmodic jerky contraction of groups of muscles) provoked by startle
vCJD
how common? prevalence? transmission? symptoms? prognosis?
main differentials?
typical age?
treatment?
type 4 prion
less common than sCJD
bovine to human transmission of BSE (in CSF or contaminated meat)
slower compared to sCJD
typical age is 29 years
duration of illness 14 months
key - peripheral pathogenesis distinct from sCJD, with prominent involvement of lymphatic/lymphoreticular tissues
main differentials - type 4 PRPsc not found in other human prion diseases
trophism for organs such as tonsils
abnormal MRI
staining FLORID PRP plaques, round amyloid core surrounded by vacouels
three causes of CJD
sporatic (sCJD)
Familial - fCJD inherited
Iatrongenic - iCJD - exposure during medical procedure
what makes prion diseases unique?
no virus particle, bacteria, fungi, parasite associated. No nucleic acid associated with infectivity. Infection still transmittable after proteins get treated. No immune response. Lead to protein only hypothesis
PRPsc can arise from…
spontaneous mutations in the PRPc gene (sCJD) or exogenous sources (cCJD)
what happens if you delete the prion gene form mice?
they do not get the disease and are otherwise healthy.
how are different PRPsc types differentitated?
through fragmentation and then run on western blot.
determined by ratio of three bands formed.
gold standard for detecting all forms of sCJD
other tests for sCJD?
biopsy - will show neuronal loss without inflammation - different from neurotrophic viruses that cause inflammation
detect 14-3-3 protein in CSF
- abnormal TR MRI
- EEG pattern of PSWC’s
sCJD is a disease of the….
elderly, over 65
vCDJ vs sCDJ?
Slower loss of brain function compared to sCJD, still rapid compared to alz and hunt
- mean duration 14 months vs 4-6 for scjd
- key point - vCJD has peripheral pathogenesis - infection of lmypoid tissue (tonsils, thymus)
- vcdj is also fatal as is
sCJD vs cCJD staining?
Important - staining is different. vCJD is stained for prion protein
With sCJD - diffuse staining
With vCJD - prion plaques surrounded by vacuoles
what happened 10 years after BSE regulations?
people started to get CJD, suggests a 10 year incubation time.
