Prion Diseases Flashcards
Rare, fatal, rapidly progressive neurodegenerative diseases that occur in humans & other animal species
Prion diseases
In prion disease, a presence of _____ within the neuropil, produces a _____ appearance
Small vacuoles; spongiform
The complex net of axonal, dendritic & glial branching that forms the bulk of central nervous system gray matter of the brain & in which the nerve cell bodies are embedded:
Neuropil
Describe prion diseases:
-Rare
-Fatal
-Rapidly progressive
Neurodegenerative diseases that occur in humans & other animals
What animal prion diseases affects cattle?
Bovine, spongiform encephalopathy
What animal prion disease affects sheep & goats?
Scrapie
Human prion diseases include: (5)
- Kuru
- Creutzfeldt-Jakob disease (CJD)
- Variant Creutzfelft-Jakob disease (Variant CJD)
- Gerstmann-Straussler-Scheinker Syndrome
- Fatal familial insomnia (FFI)
Fatal neurodegenerative disease of sheep:
Scrapie
Scrapie is demonstrated to be a _____ disorder
Transmissible
Fatal neurodegenerative disease of humans recognized since the 1920, demonstrated to be transmissible in the 1960s (humans to chimpanzees):
Creutzfeldt-Jakob Disease (CJD)
What are the early symptoms of CJD?
-memory problems
-behavioral changes
-poor coordination
-visual disturbances
What are the layer symptoms of CJD?
-dementia
-involuntary movements
-blindness
-weakness
-coma
What is the outcome of CJD?
70% of people die within 1 year of diagnosis
It was discovered during the search for the infectious agents of Scrapie & CJD, that infection agents were _____ meaning not cellular, therefore, possibly a ____
Filterable; virus
When determining what the infectious material of Scrapie & CJD was, ionizing radiation did not affect transmission of Scrapie & CJD, what does this mean?
The infectious material did not contain DNA or RNA
Because ionizing radiation did not affect the transmission of Scrapie & CDJ, the hypothesis of the 1960s concluded that the scrapie & CJD are caused by:
Solely proteins
What term was created to describe Scrapie & CJD?
Prion
What term was created to describe Scrapie & CJD,
The term prion means:
Proteinaceous infection
The cellular protein involved in prions:
PrP (prion protein)
Describe endogenous Prp:
Normal protein in the body that is NOT an disease agent
Endogenous Prp’s can adopt a couple of different confirmations:
- Normal
- Disease forming
The difference between a normal PrP & a disease-causing PrP occurs at the:
Confirmation level
What is significant about an endogenous PrP converting to prion form?
It can continue to cause other endogenous PrPs to convert to the disease causing form
What is responsible for encoding PrP protein?
PRNP gene on chromosome 20
The PrP gene displays:
Polymorphism
What do we mean when we say the PrP gene displays polymorphism?
Variance of gene sequence which results in variance of amino acid sequence
Describe an area in the PrP sequence that we may see polymorphism:
Met or Val at codon 129 of PRNP gene
What is the occurrence of seeing Met or Val at codon 129 of the PRNP gene:
Met= 60%
Val= 40%
When an individual is homozygous for either Met or Val at codon 129 of the PRNP gene, what does this mean?
They are at increased risk of disease (CJD)
The scrapie/prion form of Prp (PrPsc) is resistance to _____ & accumulates in ____
Degradation; Amyloid fibrils
PrPc (normal form of PrP) is strongly expressed in both ____ & ____ of the CNS
Neurons & glial cells
What is the function of PrPc in the CNS?
Appears to regulate ion channels & neurotransmitter receptors at the pre- & post-synaptic levels
What is the median age of death for an individuals with CJD?
68 years
What is the median age of death for an individual with a variant of CJD?
28
What is the median duration of illness for an individual with CJD?
4-5 months
What is the median duration of illness for an individual with a variant of CJD?
13-14 months
What are the clinical signs & symptoms of CJD?
Dementia & early neurologic signs
What are the clinical signs & symptoms of variant CJD?
Prominent psychiatric/behavioral symptoms; painful dysthesias; delayed neurologic signs
Describe the accumulation of PrPSC in brain tissue in an individual with CJD compared to an individual with Variant CJD:
CJD: Variable accumulation
Variant CJD: Marked accumulation
What is a clinical concern of prion diseases?
Prions may NOT be inactivated by means of routine surgical instrument sterilization procedures
The WOH & US CDC and Prevention, recommend that instrumentation used during prion cases must be:
Immediately destroyed
Secondary to destruction of instruments use in prion cases, it is recommended that ____ & ____ be used in combination to process instruments that come into contact with high-infectivity tissues:
Heat & chemical decontamination
Since the adoption of current sterilization procedures regarding prion disease instrumentation use in 1976 what have we seen?
No cases of iatrogenic transmission of CJD that been reported
