L6 Pathology Prion disease

Question 1

how is the post mortem examination carried out

Answer 1

high risk
dedicated equipment
full protective gear: visor, double gloves, safety boots

Question 2

what findings lead to protein only hypothesis

Answer 2

no viral particles detectable
no significant inflammatory or immunological reactions of the host
deposition of an abnormal protein, often in form of plaques

infectivity is associated with the protein deposits
damage to nucleic acids does not inactivate infectivity
extraction of the protein fraction abolishes infectivity

Question 3

what is Prusiner 1982 hypothesis

Answer 3

the plaque protein is the infectious agent

Question 4

what is the Weissmann 1985 hypothesis

Answer 4

the normal non-infectious protein PrP^c is encoded by the host (cellular form of PrP)and mainly expressed on neurons

Question 5

what is the protein only hypothesis

Answer 5

the infectious prion protein has the same amino acid composition, but is resistant to proteases and tend to ploymerise

Question 6

what are thermodynamic assumptions

Answer 6

there is conversion prevented by energy barrier between PrP^c and PrP^sc
or there is equilbrium

Question 7

what happens in seeding and

Answer 7

if there is an excessive production of this misfolded form, you have a seed formation and that recruits further seeds built up to an infection seed then fragments into infectious seed or amyloid

Question 8

what is not essential in template directed refolding

Answer 8

amyloid not essential for replication

Question 9

what is the definition of prion

Answer 9

Agent of transmissible spongiform encephalopathy (TSE), with unconventional properties.
The term does not have structural implications other than that a protein is an essential component

Question 10

what is the definition of PrP^c/PrP^sen

Answer 10

The naturally occurring form of the mature Prnp gene product. Its presence in a given
cell type is necessary, but not sufficient, for replication of the prion

Question 11

what is the definition of PrP^sc or PrP^res

Answer 11

Abnormal’ form of the mature Prnp gene product. Partly resistant to digestion by
proteinase K.
Believed to differ from PrPC conformationally. Often considered to be the transmissible agent or
prion.

Question 12

how many amino acids are in the PrP isoforms

Answer 12

209

Question 13

what is the primary translation product and how many anchors needed for the glycosilation

Answer 13

primary gene product with the signal peptides

3 gpi

Question 14

what happens in a mature PrP

Answer 14

primary translation/gene product matures and the signal peptide is taken off

the cellular formis protease sensitibe- breaks down into fragemnts

Question 15

what happens in PrP^sc

Answer 15

the abnormal form with misfolded proteins with same primary structure and no other amino acids is now partially resistant to proteases - can be used as detection

prp-res for resistant

Question 16

what is the corollary to the protein only hypothesis

Answer 16

Prnp knockout mice are resistant to scrapie
presence of abnormally folded protein, leads to the production of more abnormally folded protein

take awaysubstrat eshould be no more product

• this was experimentded in 1991 - generated mice

Question 17

name a sporadic form of prion disease

Answer 17

Creutzfeldt-Jakob Disease

Question 18

name hereditary forms

Answer 18

Familial CJD and Gerstmann-Sträussler-Scheinker-Syndrome

– Fatal familial insomnia

Question 19

name transmitted forms

Answer 19

Kuru (ritual cannibalism in New Guinea)
– Medical procedures (Iatrogenic CJD)
• contaminated growth hormone
• Dura mater graXs, cornea graps
• Surgical instruments, EEG electrodes
– Variant CJD (BSE epidemics

Question 20

how many polymorphism does prion gene have

Answer 20

2

Question 21

what is seen microscopically in CJD

Answer 21

neuronal loss
spongiosis
gliosis
Fine spongiform changes in the cortex, and synaptic PrP
Macrovacuoles, coarse PrP
Cortical ribbon, perineuronal net

Question 22

what gss phenotype forms plaques in PRNP gene

Answer 22

P1OL

P1O5L

Question 23

what can form in prp deposition patterns

Answer 23

gss

Question 24

where are vCJD prions detectable in BSE

Answer 24

detectable in the lymphore;cular system (e.g. tonsils, appendix),
thought to precede CNS
invasion
within the follicular dendritic cells there’s abnormal prion patients who acquire BSE

Question 25

how many glycosilation trees does the prp gene production have

Answer 25

none, 1 or 2

Question 26

where is the distribution of abnormal PrP in human tissues in body of variant

Answer 26

brain
eyes 
sympathetic ganglia
tonsil
lymph nodes
spinal cord
spleen
adrenal
rectum

Question 27

what is the clinical feature or kuru

Answer 27

progressive cerebellar ataxia

Question 28

what does kuru resemble

Answer 28

iatrogenic CJD caused by peripheral administration of contaminated growth hormone

Question 29

how can prion diseases transmit through medical procedures

Answer 29

More than 200 cases of Creutzfeldt-Jakob disease (CJD) have resulted from
treatment with human cadaveric pituitary-derived growth hormone
contaminated with prions
• Approximately 200 cases of CJD resulted from the transmission through
dura mater grafts
• Electrodes, cornea grafts, surgical instruments
• Blood transfusion

Question 30

who did studies on kuru to primates

Answer 30

The agent was previously thought to be a slow virus
• But it had rather unusual biological proper;es.
• Transmission studies were carried out in primates (Gajdusek, Gibbs, Alpers 1967)
• The findings led to the proposi;on of the protein only hypothesis (Griffith 1967)

Question 31

in what ways can the disease be iatrogenic

Answer 31

vCJD blood transfusion
gonadotroph hormone
corneal grafts
neuro-surgical instruments
dural grafts
growth hormone