B118 Prions, CJC, vCJD

Question 1

General prion disease facts

Answer 1

1) Prion: A prion is an infectious agent composed of protein in a misfolded form.

2) Prion diseases: All known prion diseases affect the structure of the brain or other neural tissue and all
are currently untreatable and fatal.

Prion diseases are associated with misfolded abnormal forms of a normal cellular protein, termed prion protein (PrPc).

Question 2

Prion protein, what is it called in normal form, pathologic form

cahracteristics of both types

Answer 2

normal protein:

• PRPc (c for cellular)
• lots of alpha helices

prion:

• PRPres - for resistant
• PRPsc - for scrapie
• lots of beta-pleated sheets
• induces conformational change in other proteins and is thus infectious
• brought on by mutations to the PRPc gene, sporadically, or due to spontaneous conformation change at very very low rates, or by induction of change by another infections prion.

Question 3

CJD, presentation, morphology and histology, prognosis

Answer 3

Sporadic in 85% of cases, and occurs in patients over 70 years.

Familial cases exist, and occur at younger ages, due to mutations in the PRNP gene, coding for PRPc

Iatrogenic cases have been clearly demonstrated due to infection from surgical tools and electrodes used in the brain of infected patients, and in contaminated preparations of human growth hormone.

Symptoms and progression.

• First subtle memory and behavioral changes
• Presents as rapidly progressive dementia
• Death occurs in 7 months after onset and there is no treatment.

Morphology:

• Death occurs rapidly, and there is little or no evidence of brain atrophy
• Pathology is only observed microscopically.
• Spongiform transformation of cortical and deep gray matter.
• Extracellular, microscopic vacuoles within the neuropil and sometimes intracellular within neuronal cell bodies
• Neuronal degeneration and reactive gliosis is evident histologically, and there are numerous small micro-cysts throughout the parenchmya - spongiform.
• There is no inflammatory infiltrate
• PrPsc is demonstrated by immunohisto stains, or by western blot.

Question 4

variant CJD,

cause, presentation, morphology histology

Answer 4

Different disease, resulting from infection by prion material from bovine spongiform encephalopathy, potentially by ingestion or by blood transfusion

The progression and presentation is similar to CDJ, with the additional presense of abudant extracellular cortial amyloid plaques.