Structure:

• All known mammalian prion diseases are caused by the so-called prion protein PrP (9)

          -PrP(C) is the endogenous properly folded form
          -PrP(Sc) the disease-linked misfolded form

• The exact structure is not known: can be formed by combining PrP(C), polyadenylic acid and lipids in a protein misfolding cyclic amplification (PMCA) (11)
• The abnormal fold is called the amyloid fold, in which the protein is aggregated into densely packed beta sheets (12)
• The polypeptide aggregates form plaques which are thought to cause "entanglement" of neurofibrils and interferes with synapse function, leading to neuron death and dementia (12)

Classification:   Each can be transmitted experimentally (2)

Infectious

• spread by consumption of infected material, latrogenic spread (organ transplant especially cornea), transfusion
• eg. Kuru, Mad Cow, Scrapie

Sporadic

• 1-2 million people are infected worldwide, shows up later in life
• evidence shows that some sporadic TSE is a result of infection

Familial

• due to autosomal dominant mutation of PrP
• inherited: at least 10-15% of total human TSE cases