Lecture 11- Prions 201 Flashcards
____ and ____ may protect against CJD
- V127
- E219K
What are the three types of genetic prion disease?
- Familial CJD
- PrP amyloidosis
- Thalamic degeneration
What are two types of PrP amyloidosis?
- GSS
- Peripheral amyloidosis
What is a type of thalamic degeneration?
Fatal Familial Insomina (FFI)
What is the pathology of GSS?
Multicentric amyloid plaques
GSS is ____ mutations but majority are ____
- 24
- P102L
What are the 4 different clinial phenotypes of GSS?
- Typical GSS described originally
- GSS with areflexia and paresthesia
- Pure dementia GSS
- CJD like GSS
What presentation do you get with GSS?
- Usually have a dominant presentation meaning they have one copy of the mutant allele, one copy of the normal allele but they both misfold
- It depends on the combination of the ratio of misfolded proteins
- Shapes of both will be slightly different (treatment target have to go for both)
What are the 4 neuropathological descriptions in GSS?
- Parenchymal PrP amyloid and prominent spongiform changes
- Parenchymal PrP amyloid and minimal or no spongiform changes
- Parenchymal PrP amyloid coexisting with severe tau neurofibrillary pathology, and absent or minimal spongiform changes
- Vascular PrP cerebral amyloid angiopathy coexisting with severe tau neurofibrillary pathology
What is GSS?
Heritable neurodegeneration
What is FFI?
Heritable syndrome of progressive sleep disturbance, autonomic changes, tremor, dysarthia, myoclonus, cognitive decline
FFI is the atrophy of the thalamus without ____ or ____
- Spongiform change
- Amyloidosis
What is the way to diagnose FFI?
- MRI, EEG and QuIC can be normal
- Need to sequence the prion gene mutation
What mutation is FFI?
D178N in cis with M129
Describe FFI in MM129 individuals
- Shorter disease (11+/- months)
- Sleep change, prominent myoclonus, autonomic dysfunction, spatial disorientation, hallucinations, weight loss
Describe FFI in MV129 individuals
- Longer disease (23+/- months)
- Early visual symptoms and ataxia, later dysarthria, seizures, bulbar symptoms
Familial Disease resembles ____ and targets the _____
- Sporadic CJD
- Thalamus
What are the presentations of VPSPr?
- Psychiatric, speech/language change, then cognitive decline
- Older onset
- Longer duration (2 years)
- MRI and EEG often normal
- Hard to pick up, essentially need autopsy
VPSPr have between ____ bands
5 and 7 fragements
What happens to the brain in VPSPr?
- Spongiform change
- PrP amyloid miniplaques
What is a prion?
- A protein that can misfold and self template
- Aggregates can spread cell to cell
- Different conformations can produce distinct phenotypes/strain characteristics
- The misfolding process leads to neurodegeneration
What two prions contribute to Alzheimers?
- Tau
- Amyloid-beta (Abeta)
What are the four types of prions?
- Abeta
- Tau
- Alpha-synuclein
- PrP
Do prions have different strains?
Yes
Why does it matter that tau and Abeta comes in different strains?
- Comes in different lengths, different combinations of these lengths can cause different shapes/conformations
- Ability to aggregate differs because of this (some fast, some slow)
- Phenotypes vary (conformation leads to pathology)
Different strains transmit different _____
Pathology
