Leeds: Prion proteins could be target for treating Alzheimer’s

Research lead

Prion proteins shot to notoriety as the infectious agents responsible for spreading new variant Creutzfeld-Jakob disease and mad cow disease. Now it transpires that normal prions produced by the body help to prevent the plaques that build up in the brain to cause Alzheimer’s disease. The possible function for the rogue proteins was discovered by a team of scientists at Leeds University in the United Kingdom, led by Professor Nigel Hooper.

Alzheimer’s and diseases like variant Creutzfeldt-Jakob Disease follow similar patterns of disease progression, and in some forms of prion disease share genetic features. These parallels prompted Hooper’s team to look for a link between the different conditions.

“Our experiments have shown that the normal prion proteins found in brain cells reduce the formation of beta-amyloid, a protein that binds with others to build plaques in the brain that are found in Alzheimer’s disease,” says Hooper.

In variant Creutzfeld-Jakob disease, the prion protein PrPc in the brain is corrupted by infectious prions to cause disease, and until now the normal function of PrPc has been unclear.

It appears that PrPc, the normal prion protein, exerts its beneficial effect by stopping an enzyme, beta-secretase, from cutting up amyloid protein into the smaller beta-amyloid fragments needed to build plaques.

Further evidence for the protective role of normal prion proteins is provided by mutated versions that are linked to genetic forms of prion disease because beta-amyloid fragments are able to form when the normal prion protein is corrupted by genetic mutation.

“The next step for our research will be to look in more detail at how the prion protein controls beta amyloid,” said Hooper. This knowledge could be used to design anti-Alzheimer’s drugs. “Theoretically, if we can find a way of mimicking the prion’s function we should be able to halt the progress of Alzheimer’s. However, there’s still a lot of work to be done in looking at levels of prions in the human system and how these may alter as we age,” said Hooper.