What Causes Prion Disease?

Prion diseases are associated with the build up in the brain (and some other organs) of an abnormal or ‘rogue’ form of a naturally occurring cellular protein, known as the prion protein. The rogue protein results from a change in shape of the normal prion protein.  Once formed in the body these rogue proteins recruit and convert more of the normal prion protein into the abnormal form, setting off a kind of chain reaction which leads to a progressive accumulation of the rogue protein.  In the normal course of events, once they have served their purpose, prion proteins are broken down by enzymes in the body.  The abnormal prions however are more resistant to this process; so they accumulate and cause damage in the brain, which interferes with normal brain functioning.  All forms of the disease are thought to be associated with an incubation period.  This is a clinically 'silent phase' during which replication of the rogue protein is thought to be taking place.

 

Genetic Susceptibility

At a particular position in the prion gene known as codon 129, there are two possible genetic types, which in turn specify the body to produce different amino acids at this position.  These amino acids are called methionine and valine, or M and V for short.  In most countries, MM and MV frequencies in the population are roughly equal (40-50%).  It has been known for some years that individuals, who are MV, are at much less risk of developing prion disease than are MM or VV individuals .