Chan

Question 1

What is the protein-only hypothesis?

Answer 1

No virus particles, bacteria, or fungi have been associated with prion diseases

No nucleic acid is associated with infectivity; agent is resistant to UV radiation and nucleases

No immune response to infection

Question 2

What are the arguments agains the protein-only hypothesis?

Answer 2

Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are also characterized by the formation of misfolded proteins resulting in neurodegeneration -skeptics argue these diseases are not infectious; thus, misfolded protein alone is not enough to transmit disease

Spongiform diseases come in distinct strains that differ in their incubation period, symptoms, and effects on different brain regions -skeptics argue that these differences are due to mutations in nucleic acid.
Long incubation time and rapid onset resemble HIV

Question 3

What is the difference between vCJD and sCJD?

Answer 3

vCJD is distinguished from sCJD by the following features:
– Type 4 PrPsc is unique to vCJD
– Can be transmitted person-to-person by blood transfusion or ingestion of
food contaminated with BSE
– A considerably younger age of onset (29 versus 65 years of age)
– Less rapid progression of illness (14 versus 5 months)
– vCJD has a peripheral pathogenesis
– Differences in neuropathology
– vCJD has tropism from lymphoid organs such as tonsils
– Detection of 14-3-3 protein in CSF is not a sensitive marker for vCJD
– Abnormal MRI signal is distinct from those obtained from sCJD patients
– EEG is abnormal, however, in contrast to a PSWCs pattern seen in sCJD patients, vCJD is associated with a slow wave pattern
– Abnormal PrP deposition in sCJD presents as diffuse staining, whereas, vCJD florid PrP plaques consist of a round amyloid core surrounded by a ring of spongiform vacuoles

Question 4

What are the safety precautions when working with prions?

Answer 4

Employ universal precautions when handling blood and cerebral spinal fluid (CSF)
Highest risk from brain, spinal cord, and eye tissues
Scrupulously avoid contact with post-mortem tissues – don’t get it into cuts or scratches on your skin
All precautions should be followed during autopsy and embalming

Question 5

What is Creutzfeldt-Jacob Disease?

Answer 5

The most frequent of human prion diseases.

Causes of CJD:

• Sporadic (sCJD), no known cause (85-95% of cases)
• Familial (fCJD), inherited genetic risk (7-10%)
• Iatrogenic (iCJD), exposure during medical procedures (<1%)

sCJD can not be transmitted person-to-person by blood transfusion or meat contaminated with BSE

sCJD is NOT related to human “mad cow disease”

Brain biopsy remains the gold standard and only definitive diagnostic test for all forms of CJD