Prions

Question 1

what are the common pathologies seen in transmissible spongiform encephalopathies

Answer 1

multifocal spongiform changes
amyloid
astrogliosis
neuronal loss

Question 2

what is the prion protein? where is it found?

Answer 2

209 amino acid glycoprotein that is expressed on the cell surface and is anchored ther by FA

in a single exon on chrom 20

highly expressed in NEURON and LYMPHOCYTES

Question 3

nml function of PrPc

Answer 3

inhibit BACE1 activity which inhibits the formation of beta amyloid

Question 4

differences in __ cause PrP-Sc to be ____

Answer 4

folding –> resistant to proteases

Question 5

how does a folding difference lead to a diseased state?

Answer 5

aggragates form; these are unstable and cause the neuron to undergo APOPTOSIS

Question 6

mice lacking ___ are resistant to prion infection. Significance?

Answer 6

PrP-C, meaning PrP-C is needed for the formation of PrP-Sc

**PrP-Sc forms when an intermediate of PrP-C interacts with another PrP-Sc which acts as a template for all the other abn proteins = CHAIN REACTION

Question 7

what explain the late onset of sporadic CJD

Answer 7

PrP-C is greatly favored and it takes a long tine for the rare, pathogenic (PrP-Sc) to form (age dept mutation?)

Question 8

what dictates the final conformation a prion protein assumes

Answer 8

template prion NOT the amino acid sequence of the protien

Question 9

What is scrapie and what is its significance to human prion disease?

Answer 9

subacute, progressive ataxia in sheep and goats that showed transmission occurred via the alimentary tract

Question 10

clinical features of Creutzfeldt-Jakob disease (CJD)

Answer 10

dementia, myoclonus, ataxia, akinetic mutism

Question 11

most common type of CLD (sporadic, familial, or iatrogenic)

Answer 11

sporadic

Question 12

average age of onset in sporadic and familial CLD

Answer 12

sporadic = 60
familial = 45 to 50

Question 13

who lives longer after diagnosis, those with sporadic or familial CJD

Answer 13

familial (2-4 yrs vs 1 yr)

Question 14

mode of inheritance for familial CJD

Answer 14

AD

there are specific mutations in the prion protein that appear to facilitate the conversion of C to Sc

Question 15

where do spongiform changes take place with prion disease

Answer 15

cerebellum

Question 16

what diagnostic fining is specific to CLD

Answer 16

periodic complexes on EEG

Question 17

clinical features of GSS dz

Answer 17

gait abn and ataxia

DEMENTIA IS LESS COMMON

Question 18

etiology of GSS

Answer 18

mutation at codon 102 of prion protein and has AD pattern of inheritence

Question 19

clinical features of FFI

Answer 19

sleep disturbances and autonomic dysfunction

Question 20

etiology of FFI

Answer 20

mutation in codons 129 and 178 with AD pattern of inheritance

Question 21

vCJD is the same dz as

Answer 21

mad cow (aka BSE)

Question 22

etiology of vCJD

Answer 22

consuption of contaminated beef (also blood transfusions noted)

Question 23

sources of iatrogenic CJD

Answer 23

dural and corneal grafts

pituitary derived hGH

Question 24

avg age on onset for vCJD

Answer 24

29!!! VERY YOUNG (younger than familial/genetic etiologies= familial CJD, FFI, GSS)

Question 25

clinical characteristics of vCJD

Answer 25

anxiety, depression, visual problems

Question 26

all pts with vCLD had what gene polymorphism in common

Answer 26

homologous for menthionine at codon 129 of PrP

Question 27

histo changes unique to vCJD

Answer 27

florid plaques and spingiform changes in BASAL GANGLIA

Question 28

subcellular location of PrPc vs PrPSc

Answer 28

C = cell surface and Sc = intracellular vesicles

Question 29

which prion diseases are assc with plaques?

Answer 29

GSS and vCJD

Question 30

which prion diseases are assc with cerebellar spongiform changes

Answer 30

CJD, GSS

*vCJD are in basal ganglia