Prions Flashcards Preview

Neurology > Prions > Flashcards

Flashcards in Prions Deck (40):
1

TSE's?

Transmissable Spongiform Encephalopathy

2

What causes TSEs?

Prions (infectious proteins)

3

TSE disease process

Long incubation period but then rapidly progressive. Usually leads to a fatal dimentia
Pathology shows multifocal spongiform changes

4

Are there amyloid plaques present in TSE

not usually

5

Inflammation in TSE (transmissable spongiform enceph)

minimal

6

Human TSE

-kuru
-creutzfeld-jakob
-Gertsmann Straussler Scheinker disease
- Fatal familial insomnia
- Variant CJD

7

Animal TSE

Scrapie (seen in sheeps and goats)
Bovine spongiform encephalopathy (BSE)
Chronic Wasting Disease (deer and elk)

8

Agents that cuase TSEs are resisitant to what

Regular virus treatments which damage nucleic acids.

9

Prion stands for

Proteinacious infectious particles

10

Prion protein is highly conserved among humans and animals

KNOW

11

where is the prion protein encoded>

on a single axon on human chromosome 20

12

Prion protein is highly expressed where

neurons and lymphocytes

13

Prion protein final product

a 209 amino acid glycoprotein that is anchored to cell surfaces by a fatty acid

14

WHat are the two general forms of prions

The physiologic type: PrPc

The patologic type: PrPsc or PrP res
Stands for PrP scrapie or PrP resistant

15

KNOW PrPc and PrPsc can have identical sequences yet they are different because of what

They way they fold.

PrPsc is unusually stable and only partially degraded by proteases. Aggregates in cell cytoplasm and leads to neuron apoptosis

16

Remember...you must express PrPc in order to contract disease. ALso remember that there are probably chaperone proteins involved in this process since simly mixing PrPsc and PrPc together doesnt generate scrapie protein

ok

17

What the fuck is the scrapie disease

- subacute, progressive ataxia of sheep
- first found at one year of age in lymphatics and tissues
- by 2 yrs the brain is infected

18

First documented human TSE

Kuru

19

Most common human TSE

Creutzfeld Jakob (CJD)

20

Three forms of CJD

sporadic- most common
Iatrogenic
Familial

21

classic CJD quadrad

-Dementia
- Myoclonus
- Ataxia
- Mutism

22

Sporadic CJD onset age

around 60

23

Mean survival time for sporadic CJD

only 5-8 mos

24

Cause of sporadic CJD

pretty much unknown

25

How do you get iatrogenic CJD

Dural grats
Corneal grafts
HGH

NOT BLOOD TRANSMISSION

26

Familial CJD inheritance

Auto dominant

age of onset 45-50
survival 2-4 yrs

27

CJD diagnosis

- CLinical course: rapid dementia and myoclonus
- histology shows spongiform change and no amyloid which rules out alzheimers

- Check CSF to rule out tertiary syphillis

28

Gertzman Schausler Shanker (sp?) follows what inheritance patterns

AD

29

What mutation is GSS associated with

codon 102 of PrP

30

Clinical features of GSS

avg age of onset is 48
mean time to death is 5 years
gait abnormalities and ataxia
dementia is less common

31

KNOW>..GSS shows amyloid plaques and spongiform changes

ok

32

FFI inheritance

AD

33

Clinical features of FFI

- sleep disturbaces
- autonomic dysfunction

34

histo of FFI

no spongiform changes. just neuronal loss

35

Variant CJD

NEW!! found in UK in 90's

36

the causative agent of CJD is the same as what

The same as BSE (mad cow). So it came from contaminated beef or blood transfusion which is different that the CJD we discussed earlier

37

One major difference between regular CJD and variant is

Regular affects pretty much only the CNS

Variant = CNS, retina, DG, bone marrow, tonsils, spleen, lymphnodes, appendix, blood

Also:
Age of onset is 29 in variant (compared to 60)
mean survivial is 14 in variant (compared to 5-8)
SEnsory abnormalities , anxiety, depression

38

ALL INDIVIDUALS WITH vCJD were homozygous for

methionine at position 129 of Prp

39

Diagnosis of vCJD

prion positive tonsil biopsy
histology shows spongiform changes in basal ganglia...flower appearance

40

how do you properly sterilize graft equit to protect from iatrogenic CJD

soak in 1 M sodium hydroxide for an hour followed by autoclave at 134 C