Prions Flashcards
What is sporadic Creutzfeldt-Jacob Disease? How is it NOT transmitted?
sporadic - no known cause
NOT transmitted person-to-person by blood transfusion
NOT transmitted by meat contaminated with BSE
what are sCJD, fCJD, and iCJD?
sporadic Creutzfeldt-Jacob Disease - no known cause
familial Creutzfeldt-Jacob Disease = inherited genetic risk
iatrogenic Creutzfeldt-Jacob Disease = exposure during medical procedures
What is spongioform encephalopothy?
prion disease
How is sCJD different from Alzheimer’s?
sCJD has more rapid progression of memory loss
What are the two cardinal clinical manifestations of sCJD?
rapidly progressive mental deterioration
myoclonus - provoked by startle
What led to the protein-only hypothesis for prion diseases?
- prion diseases not associated with virus particles, bacteria, fungi
- infectivity not associated with nucleic acid; prions are resistant to UV radiation and nucleases
- no immune response to infection
What do skeptics say against the protein-only hypothesis for prion diseases, which are characterized by protein misfolding, similar to to Alzheimer’s, Parkinson’s, and Huntington’s?
the other diseases diseases are not infectious, but prions are
misfolded protein is not enough to transmit disease
What do skeptics say about the fact that spongioform diseases come in distinct strains which differ in their incubation period, symptoms, and effects on different brain regions?
differences are due to mutations in nucleic acids
long incubation time and rapid onset resemble HIV
What is PrP^c?
Cellular form of Prion Protein - membrane glycoprotein
Misfolding causes encephalopathy
What does PrP^c become after misfolding? What does this lead to?
PrP^sc - Scrapie form of Prion Protein
Prion disease
How can PrP^sc arise?
mutation exogenous sources (meat, blood)
How were 4 types of human PrP^sc detected?
digestion with proteinase K yielded 3 PrP bands
What is the model for Prion Self Replication?
Seed (nucleus) recruits PrP^c (native conformers) and converts them to PrP^sc (prion conformers)
seed increases in size –> amyloid fibre
fragmentation –> liberates new ends to allow for amplification; allows dissemination of infectious material
What is the diagnostic test for all forms of CJD?
brain biopsy
What three things characterize sCJD?
accumulation of PrP^sc
neuronal loss without inflammation
spongioform change
What is sCJD treatment and prognosis?
no treatment
median disease lasts 5-6 months
death after one year
What is a type 4 prion which represents bovine-to-human transmission of BSE?
variant Cruetzfeldt-Jakob disease (vCJD)
In what body parts of cattle is vCJD not found?
muscle
milk
How is vCJD different from sCJD in clinical presentation?
vCJD has slower onset of loss of brain function
what is the difference between detection of 14-3-3 protein in cerebral spinal fluid for sCJD and vCJD?
sensitive marker for sCJD
not for vCJD
Can an abnormal MRI result be used to distinguish sCJD from vCJD?
yes - both are abnormal, but distinct
What is the difference between periodic synchronous sharp wave complexes (PSWCs) seen via EEG in vCJD versus sCJD?
sCJD had sharp wave complexes
vCJD has slow waves
Which form of CJD appears as diffuse staining?
sCJD
Which form of CJD stains as a round amyloid core surrounded by a ring of spongioform vacuoles?
vCJD
How does the mean onset age for vCJD compare with that of sCJD?
vCJD = 29 sCJD = 65t
What is BSE?
Bovine spongioform encephalopathy
What sparked the peak of the BSE epidemic?
ban on ruminant feed
Which type of CJD can be transmitted from person-to-person by blood transfusion or ingestion of food contaminated with BSE?
vCJD
Which type of CJD has a peripheral pathogenesis (in tonsils, thymus, adrenal glands, lymph nodes, terminal ileum appendix, rectum)?
vCJD
Which sites of symptoms do sCJD and vCJD share?
brain eyes spinal chord muscle spleen
Why is secondary latent transmission of vCJD a potential concern?
still carried in UK population
average incubation period of 20-3- years
