Prions

Question 1

What is found in a brain biopsy of someone with Kuru?

Answer 1

Formation of amyloid plaques and spongiform encephalopathy due to vacuolation of neurons.
- death is certain in 6-12 months

Question 2

What are the initial symptoms of Kuru?

Answer 2

Myoclonic jerks and slurred speech and uncontrollable fits of laughter

Question 3

What do CMB and cultures of someone with Kuru show?

Answer 3

Nothing

it is unremarkable and nothing grows on the cultures

Question 4

Why are infectious agents of the brain so hard to irradiate?

Answer 4

Resilience too

• boiling at 30 min
• 60 days of freezing
• Formaldehyde, carboxylic acid and chloroform
• severe dryness
• intense UV
• nuclease digetions
• smaller than virus
• Sensitive to high levels of proteases

Question 5

What is PrPc?

Answer 5

Ubiquosly expressed glycoprotein involved in cell growth and maintenance
- has an alpha helix

Question 6

What is PrPsc?

Answer 6

Is a very stable isoform of the same protein that is infectious because it can convert normal PrPc to amyloids.
- contraine beta sheets instead of alpha helix

Question 7

What are amyloids?

Answer 7

Fibrous protein deposits often ass. with disease

• there is PrP protein in prion disease
• fiber made of Beta-sheet stain with Congo Red
• amyloid initiate unfolded protein response and increase vacuolation

Question 8

Is there there a single test to Dx CJD?

Answer 8

No

- get LP for meningitis and CT for tumor or other pathology

Question 9

What would be positive on labs/images based on Nation surveillance center of prion disease?

Answer 9

CSF: Elvation of protein 14-3-3 marking of neuronal degen
EEG- periodic sharp waves
MRI: High intensity in Striatum and pulvinar thalamus

Question 10

What other tests would be positive with a patient with CJD?

Answer 10

Biochem: western blot shoes PrPsc with proteinase digestion
DNA: Mutations of PRNP gene
Brain Biopsy: Spongy change- not really done since its not treated
- of note tissue can be given to mouse to see its infectivity

Question 11

Is there a risk of getting CJD from chronic wasting disease?

Answer 11

Prions of this disease can be found in urine, feces, saliva and ground water and can cross the BBB
- however humans are resistant to CWD which is found in elk and deer (which there is horizontal transfer between)

Question 12

Compare AD and CJD?

Answer 12

• Similar symptoms
• Progression is way different with CJD is fast and Ad is low as far as build up of plaque
• AD- 60 and CJD-20-30 years old average onset
• CJD is infectious and AD is not
• Both form amyloids but different proteins.

Question 13

What are the human prion diseases?

Answer 13

1. Kuru
2. Varient CJD
3. Iatrogenic CJD
4. Familial CJD
5. Sporadic- which is the most common (idiopathic)

Question 14

What is Variant CJD

Answer 14

consumption of meant contaminated with Bovine spongiform Encephalopathy
- increased susceptibility ot vCJD if you have a variant in codon 129 of PRNP

Question 15

Iatrogenic CJD

Answer 15

Cadaver pituitaries, contaminate of grafts or surgical instrument and corneal transplants and even blood.

Question 16

Familial CJD

Answer 16

Large number of mutations in PRNP gene with diff disease phenotypes

• Gerstmann-Straussler-Scheinker syndrome
• Familial fatal insomina

Question 17

What are the symptoms of CJD?

Answer 17

dementia
behavioral changels
lack of coordination
visual disturbances