Prions

Question 1

Definition of prion

Answer 1

infectious protein

Question 2

Different animals can have prion diseases. In humans, there are 5 recognized ones.

Answer 2

1. Kuru
2. Fatal Familial Insomnia
3. Gerstmann-Stassler-Scheinker syndrome
4. variant Cretzfeldt-Jacob Disease (vCJD)
5. Creutzfeldt-Jacob Disease (CJD)

Question 3

CJD is the most common prion disease in humans. What are some causes?

Answer 3

1. sporadic (sCJD) -no known cause accounting for 85-95%)
2. familial (fCJD) -inherited risk (7-10%)
3. iatrogenic (iCJD) -exposure during medical procedures (<1%)

Question 4

Is sCID related to human “mad cow disease”

Answer 4

No, it is not what we know today as mad cow disease

Question 5

T/F: sCJD can be transmitted person-to-person by blood transfusion or meat contaminated with BSE.

Answer 5

False

Question 6

Symptoms of sCJD

Answer 6

• spongiform encephalopathy
• loss of brain function resembles Alzheimers, but occurs RAPIDLY
• complete dementia usu. occurs by the 6th month
• death occurs within one year of symptom onset

Question 7

What are the two cardinal symptoms and signs of sCJD?

Answer 7

1) mental deterioration -delirium, dementia, mood changes

2) myoclonus -muscle twitching, provoked by startle

Question 8

What causes prion diseases?

Answer 8

Protein-only hypothesis (not caused by microbes b/c lack of immune response)

Question 9

Prions are encoded by the host by which gene?

Answer 9

PrPc gene (cellular form) is involved in maintaining brain’s white matter, neuron formation.

Question 10

Protein misfolding converts PrPc to

Answer 10

PrPsc (scrapie form) -beta sheet

Question 11

T/F: PrPsc can be experimentally transmitted to animals

Answer 11

True

Question 12

There are 4 types of PrPsc. How can you tell them apart?

Answer 12

Different results when in proteinase K

• Type 1 is associated with sCJD
• Type 4 is associated with vCJD

Question 13

How to diagnose prion diseases?

Answer 13

-Brain biopsy using hematoxylin and eosin stain of thin brain section

Question 14

How to characterize sCJD in biopsy?

Answer 14

1) spongiform change
2) neuronal loss w/o inflammation
3) accumulation of PrPsc

Question 15

Electroencephalography (EEG) and MRI are normal or abnormal in someone with sCJD?

Answer 15

Abnormal

Question 16

T/F: sCJD was higher among children.

Answer 16

False; sCJD is higher among the older population

Question 17

Does sCJD seem to affect one racial group over another?

Answer 17

yes, whites

Question 18

vCJD is associated with BSE (mad cow disease). What type of prion is it?

Answer 18

Type 4 prion

Question 19

vCJD is transmitted bovine-to-human transmission. If muscle and milk are contaminated with BSE, can one get vCJD?

Answer 19

Yes

Question 20

Brain deteriorates faster or slower in vCJD than in sCJD?

Answer 20

Slower in vCJD, but still rapid in comparison to Alzheimer’s. (12 months for vCJD vs 4-5 months for sCJD)

Question 21

Major difference between vCJD and sCJD is

Answer 21

vCJD has a peripheral pathogenesis with prominent involvement of lymphoreticular tissues (tonsils, spleen)

Question 22

Will patient with vCJD have abnormal or normal EEG and MRI?

Answer 22

Abnormal

Question 23

Absolute method to differentiate btw vCJD and sCJD?

Answer 23

Brain biospy

-vCJD will have brown amyloid cores surrounded by vacuoles which are absent in sCJD

Question 24

T/F: vCJD affects a lot younger people than sCJD

Answer 24

Yes, avg age of people affected by vCJD is around 29 compared to 60ish in sCJD.

Question 25

vCJD epidemic peaked between

Answer 25

1999-2000 (about 8 yrs after the BSE epidemic)

Question 26

Since 1996, CDC has only received how many confirmed patients of vCJD?

Answer 26

3 patients

Question 27

Why do we need to be aware of vCJD?

Answer 27

About 1 in 2000 people in UK carry the vCJD-causing prion. The incubation period might be 20-30 years. May be a problem in the future.

Question 28

T/F: Prions are highly resistant to disinfectants, heat, UV radiation, ionizing radiation, and formalin.

Answer 28

True