Prion clinical Flashcards
What is the earliest known prion disease?
Scrapie
What is unique about prion disease?
- They can develop spontaneously
- They can be inherited
- They can be acquired
What does a prion mean?
“A small proteinaceous infectious particle”
Three steps for prion pathology?
Prion conversion (PrPc to PrPsc) (alpha to beta structure) –> accumulation –> spread
Prion pathology end stage?
Spongiform change, neuronal loss, astrocytosis (inflammation of astrocytes); accumulaiton fo PrPres(resistant to protease)
What type of plaques are formed with sCJD, vCJD, and GSS?
- SCJD –> spontaneous spongiform
- vCJD –> variant, concentraed plaques, spongiform around
- GSS –> Genetic, multicentred plaques
Define prion strain
A specific form of misfolded PrPSc that reproduciley causes a specific phenotype of disease
Both ___ and ___ of prion aggregates influence disease phenottype
Size and shape
How is prion disease layed out?
- 1-2million / year incidence
- 90% sporadic
- 10% genetic (familial CJD; PrP amyloidosis; Thalanmic degeneratioN)
- 1% Acquired (kuru, vCJD, Iatrogenic)
Describe sporadic CJD
- ALWAYS FATAL
- Peak incidnece at 7th decade
*Ataxia, visual symptoms, dementia, myoclonus - Akinetic mutism (cannot move)
- Average time of death 4-6months after onset
How is sporadic CJD diagnosed?
Definite: Autopsy only; codon 129 status can give us clues (via glycoform ratio)
True or false: V127 E219K may protect against CJD?
true
What are Gerstmann Straussler Scheinker (GSS) and Peripheral amyloidosis?
Types of PrP amyloidoses (genetic prion disease)
Describe GSS
- Early 50s, early ataxia, late cog. decline, motor/parkinsons feautres
- Longer duration (6years)
- Multicentred amyloid plaques
- Majority mutations P102L
What are the clinical phenotypes of GSS?
- Typical
- GSS w/ areflexia and paresthesia
- Pure dementia
- CJD-like GSS
Variability determiend by ratio of misfolded Prp and WT Prp protein
What type of genetic prion disease is fatal familial insomnia (FFF) under?
Thalamic degeneration
Describe FFF
- Progressive sleep disturbance, autnoic changes, tremor, dysarthia, ataxia, myoclonus
- Dementia
- 1 year duration
- NO SPONGIFORM or AMYLOIDOSIS and thalamus atrophy
- Transmissable to mice
Genetics of FFF?
- Mutation in prion protein
- Caused by D178N, however has to be on same allele as M129
- If it is in cis with V129 –> familial CJD phenotype
- MM129 makes faster disease, V129 slower
Must test for PRNP mutation for diagnosis
Why are women and children most affected w/ kuru?
Portions of person consumed was varied: women and children got brain, men got mm.
Does the presence of PrpSc (scrapie) equal infectivity?
No, it is dose dependent
Has Prpsc been detected in dura mater?
No, but probably contamintation has led to transmission in dura transplants
growth hormone graft can also spread PrPsc
Is CJD transmitted sexually or vertically?
No, also no increase incidence in healthcare workers
two researchers did die in lab due to mad cows disesase
Is PrpSc transmissable via CSF?
No
can be detected in csf using RT-QuIC
What is mad cow disease a part of?
Variant CJD (from acquired cjd) - probably acquired through scrapie which is reprocessed in the feed of animals -
not many cases ~ 232 world wide
How do proteins cross species barrier?
- Overlap of various protein types
- Adaptation –> overlap w/ other hosts
Define strains
As a prion isolates taht consistenyl induce a specific disease phenotype, pathology and incubation period in a given house – many shapes can be present in single strains
conformational drug resistance = orions adapting to diff. shapes
Strain selectivity –> have to target ALL strains
CWD prions adapy faster than BSE
