Lecture 11- Prions 201

Question 1

____ and ____ may protect against CJD

Answer 1

• V127
• E219K

Question 2

What are the three types of genetic prion disease?

Answer 2

1. Familial CJD
2. PrP amyloidosis
3. Thalamic degeneration

Question 3

What are two types of PrP amyloidosis?

Answer 3

1. GSS
2. Peripheral amyloidosis

Question 4

What is a type of thalamic degeneration?

Answer 4

Fatal Familial Insomina (FFI)

Question 5

What is the pathology of GSS?

Answer 5

Multicentric amyloid plaques

Question 6

GSS is ____ mutations but majority are ____

Answer 6

• 24
• P102L

Question 7

What are the 4 different clinial phenotypes of GSS?

Answer 7

1. Typical GSS described originally
2. GSS with areflexia and paresthesia
3. Pure dementia GSS
4. CJD like GSS

Question 8

What presentation do you get with GSS?

Answer 8

• 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)

Question 9

What are the 4 neuropathological descriptions in GSS?

Answer 9

1. Parenchymal PrP amyloid and prominent spongiform changes
2. Parenchymal PrP amyloid and minimal or no spongiform changes
3. Parenchymal PrP amyloid coexisting with severe tau neurofibrillary pathology, and absent or minimal spongiform changes
4. Vascular PrP cerebral amyloid angiopathy coexisting with severe tau neurofibrillary pathology

Question 10

What is GSS?

Answer 10

Heritable neurodegeneration

Question 11

What is FFI?

Answer 11

Heritable syndrome of progressive sleep disturbance, autonomic changes, tremor, dysarthia, myoclonus, cognitive decline

Question 12

FFI is the atrophy of the thalamus without ____ or ____

Answer 12

• Spongiform change
• Amyloidosis

Question 13

What is the way to diagnose FFI?

Answer 13

• MRI, EEG and QuIC can be normal
• Need to sequence the prion gene mutation

Question 14

What mutation is FFI?

Answer 14

D178N in cis with M129

Question 15

Describe FFI in MM129 individuals

Answer 15

• Shorter disease (11+/- months)
• Sleep change, prominent myoclonus, autonomic dysfunction, spatial disorientation, hallucinations, weight loss

Question 16

Describe FFI in MV129 individuals

Answer 16

• Longer disease (23+/- months)
• Early visual symptoms and ataxia, later dysarthria, seizures, bulbar symptoms

Question 17

Familial Disease resembles ____ and targets the _____

Answer 17

• Sporadic CJD
• Thalamus

Question 18

What are the presentations of VPSPr?

Answer 18

• 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

Question 19

VPSPr have between ____ bands

Answer 19

5 and 7 fragements

Question 20

What happens to the brain in VPSPr?

Answer 20

• Spongiform change
• PrP amyloid miniplaques

Question 21

What is a prion?

Answer 21

• 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

Question 22

What two prions contribute to Alzheimers?

Answer 22

• Tau
• Amyloid-beta (Abeta)

Question 23

What are the four types of prions?

Answer 23

1. Abeta
2. Tau
3. Alpha-synuclein
4. PrP

Question 24

Do prions have different strains?

Answer 24

Yes

Question 25

Why does it matter that tau and Abeta comes in different strains?

Answer 25

• 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)

Question 26

Different strains transmit different _____

Answer 26

Pathology