Neuro (Test 2) - Lect 7 - Prion Dz

Front 1

Transmissible Spongiform Encephalopathies cause problems due to

Back 1

failure to clear a protein (prion) leads to neuronal death

Front 2

what is the major distinguishing key of prion diseases

Back 2

transmissibility of a protein can lead to dz in other ppl

Front 3

what structure of prion is damaging to a host? what is importance about this form?

Back 3

B-sheet (aberrant form)

Aberrant forms are resistant to degradation, and are non-immunogenic to host

Front 4

common pathogenesis of Creutzfeld-Jacob Disease (CJD)

another important way?

Back 4

spontaneous conversion from alpha to beta prions

passed by person to person (reusing surgical tools, eating mad cow beef)

Front 5

man hunts a deer and wants to take it home and eat it. If he is in CO, WV or a few other places what dz does he have to worry about?

Back 5

Chronic wasting disease (CWD, deer and elk)

Front 6

all ppl who had nvCJD had changes where

Back 6

homozygous methionine at codon 129

Front 7

Rapidly progressive dementia and myoclonus. Death within year of onset. Due to an infective protein

Back 7

Creutzfeld-Jakob Disease

Front 8

what 2 ways can you distinguish mad cow (nvCJD) from sporadic CJD?

Back 8

ncCJD: “florid” plaque

other finding is “Pulvinar sign” in MRI

Front 9

what are prion proteins?

Back 9

small proteins, expressed primarily in neurons, and inserted into neuronal cell membranes

Front 10

what chromosome are prion proteins encoded on?

What is the gene and how many copies of the gene are there?

Back 10

1. Encoded on chromosome 20


2. CPRNP gene (single copy)

Front 11

describe the pathogenesis of prion dz (i.e., the protein conformational change that occurs)

Back 11

conversion of normal prion structure to abnormal:

alpha helix ---> beta sheet

Front 12

list the 3 causes that can lead to the development of abnormal prion protein and thus disease

Back 12

1. genetic (inherited or spontaneous mutation: point mutation, insertion, deletion)

2. incorrect post-translational modification

3. "spontaneous" conversion

Front 13

describe:

1. normal degradation of a prion protein

2. what occurs with degradation of mutated prion protein

3. what occurs from an infection of a prion protein

Back 13

1. Normal (PrP^sen) --> proteolysis --> degradation

2. Mutated (PrP^res) --> incomplete proteolysis --> amyloid

3. Infection: mutated + normal protein --> (2) mutated proteins --> amyloid

Front 14

1. Creutzfield-Jacob Disease (CJD) can be caused by what 2 types of mutations?

2. CJD due to infection are associated with what 3 things?

3. CJD causes what type of neurologic disorder

Back 14

1. Inherited or somatic mutation

2. Infection
a) Surgical instruments
b) Dura mater grafts
c) Human Growth hormone

3. Pre-senile dementia

Front 15

New variant CJD (nvCJD) results via?

Back 15

infection via prion-contaminated beef

Front 16

1. Gerstmann-Straussler Scheinker Disease (GSS) is caused by what type of mutation?

2. What neurologic problems does it cause?

Back 16

1. Inherited mutation

2. Progressive ataxia/dementia

Front 17

1. Fatal Familial Insomnia (FFI) is caused by what type of mutation?

2. Which part of the brain are the abnormal proteins found?

3. What neurological problems does it cause?

Back 17

1. Inherited mutation; rare somatic mutations, spontaneous conversions.

2. Thalamus

3. Intractable insomnia, dementia.

***Rare somatic mutations, spontaneous conversions

Front 18

Kuru results due to what?

Back 18

Ritualistic cannibalism

***(Fore’ people, New Guinea)

Front 19

what is the pathogenesis of Scrapie (sheep)

Back 19

sheep --> sheep infection via blood, placenta

Front 20

Bovine spongiform encephalopathy (BSE) results from what?

Back 20

Infection via sheep/cattle meat and bone meal

Front 21

Transmissible mink encephalopathy (TME) is found in what type of animals

What is the pathogenesis of this disease?

Back 21

1. Captive animals.

2. Infection via sheep/cattle meat

Front 22

Chronic wasting disease (CWD, deer and elk) is spread to humans via what?

how is CWD initially spread to deer and elk?

Back 22

1. Current mechanism of spread unknown

2. Initial infection via sheep (blood) contaminated grasses

Front 23

CJD can result in slightly different diseases due to what?

Also describe what is different

Back 23

1. Mutations (point, insertion, deletion) at **different locations** in the prion gene (250 codons, chromosome 20)

2. results in different:
a) Location
b) Onset
c) Symptomatology
d) Duration

Front 24

flip to see the where the different prion diseases affect the brain

Back 24

Front 25

mutation for Sporadic CJD (85%) occurs at what codon?

what does this lead to?

Back 25

1. Codon 129

(*normal*, Met/Val)

Front 26

mutation for Familial CJD (5%) occurs at what codon(s)?

what does this lead to?

Back 26

Codon 200 (178, 208, 210)

(Glu --> Lys)

Front 27

mutation for GSS occurs at what codon(s)?

what does this lead to?

Back 27

Codon 102 (105, 117, 145, 198)

(Pro --> Leu)

Front 28

mutation for FFI occurs at what codon(s)?

what does this lead to?

Back 28

Codon 178

(Asp --> Asn)

Front 29

mutation for nvCJD (infection with bovine prion) occurs at what codon(s)?

what does this lead to?

Back 29

Codon 129

***determine susceptibility...... in all cases, homozygous mehtionine

Front 30

mutation for nvCJD protection (Japanese) occurs at what codon(s)?

what does this lead to?

Back 30

Codon 219

(Glu --> Lys)

Front 31

What is the age of onset for CJD? What is seen on microscopy? What is seen clinically? What is the worldwide frequency?

Back 31

1. onset 60-65 yrs

2. microscopy: Progressive vaculoation, degenteration of brain

3. Rapidly progressive dementia and myoclonus (death within year of onset)

4. Occurs in low frequency worldwide (1/million, 15/million over age 60)

*** Familial, sporadic (85%) and acquired forms (brain biopsies, corneal transplants, pituitary growth hormone, dura mater grafts, ingestion of contaminated meat).

Front 32

in England/UK how is nvCJD passed to human?

Back 32

Passed to human by ingesting beef from cattle w/ bovine spongiform encephalopathy (damn Brits)

Front 33

describe what is seen on post mortem histopath of nvCJD pts

Back 33

"florid" plaque of nvCJD

Front 34

what protein is detectable in the CSF in sporadic CJD?

what protein is found to be elevated in nvCJD

Back 34

1. 14-3-3 protein (less/later on in nvCJD)

2. INC CSF tau protein

Front 35

(nvCJD) - after a tonsillar biopsy is done what lab test preformed to look for the BSE prion?

What is seen on MRI

Back 35

1.Western Blot assay (humans and animals)

***New blood test developed (2011), not yet available

2. "Pulvinar sign" on MRI

Front 36

classic CJD vs. nvCJD:

median age of death

Back 36

cCJD - 68 yo

nvCJD - 28 yo

Front 37

classic CJD vs. nvCJD:

median duration of illness

Back 37

cCJD: 4-5 months

nvCJD: 13-14 months

Front 38

classic CJD vs. nvCJD:

signs and symptoms

Back 38

cCJD - dementia; early neurologic signs

nvCJD -
a) prominent psychiatric/behavioral sym.
b) abnormal physical sensations
c) delayed neurologic signs

Front 39

classic CJD vs. nvCJD:

periodic spharp waves on electroencephologram

Back 39

cCJD: often present

nvCJD: absent

Front 40

classic CJD vs. nvCJD:

agent in lymphoid tissue

Back 40

cCJD: not readily defected

nvCJD: readily detected

Front 41

classic CJD vs. nvCJD:

immunohistochemical analysis of brain tissue

Back 41

cCJD: variable accumulation

nvCJD: marked accumulation of protease resistant prion protein

Front 42

classic CJD vs. nvCJD:

florid plaques

Back 42

cCJD: rare or absent

nvCJD: large number

Front 43

classic CJD vs. nvCJD:

Pulvinar sign on MRI

Back 43

cCJD: not reported

nvCJD: present >75% of cases

Front 44

classic CJD vs. nvCJD:

INC glycoform ration on immunoblot analysis of protease-resistant prion protein

Back 44

cCJD: not reported

nvCJD: marked accumulation of protease-resistant prion protein

Front 45

classic CJD vs. nvCJD:

treatment

Back 45

none currently

non-specific for pain, myoclonus, other symptoms