Glowing molecule detects prion diseases

4 December 2007

An international team of researchers has developed a method of identifying prion and other defective-protein diseases using a fluorescent molecule that changes colour according to the disease present.

Prions are the infectious compounds behind diseases such as mad cow diseases, while other defective-protein diseases are implicated in diseases such as Alzheimer's.

The method, reported in the journal Nature Methods (1), is based on a fluorescent molecule, a so-called conjugated polymer, which was developed at Linköping University in Sweden.

The research team infected genetically identical laboratory mice with BSE, scrapie (which afflicts sheep), and CWD (chronic wasting disease or 'mad elk disease', which is epidemic in the central US) for several generations in a row.

Gradually, new strains of prions emerged, making the diseases more fatal to the mice. Tissue samples from mice were examined using a fluorescent molecule that binds with prions. This is detected by a shift in colour.

By tweaking the molecule, the team has been able to get it to show different colours depending on the strain of the prion — each of which has a different structure.

This is an important difference compared with other techniques used to find prions, such as antibodies and the well-known stain Congo red.

The technique has also proven to work well on tissue sections from dead animals, such as cows infected with BSE. Now the scientists want to move on and look for alternative sample-taking methods for diagnosing and tracking prion diseases in humans in early stages.

Mad cow disease (BSE) has caused the death of more than 200,000 cattle and 165 people in the UK, but has now abated. Other prion disorders, however, are on the rise, and there is concern that new strains will infect humans. Prions are not readily transmittable from species to species, but once they have broken through the species barrier they can rapidly adapt and become contagious within the species.

Intensive work is now underway to find new, more sensitive methods for detecting these potentially deadly protein structures and distinguish between various strains.

The new method could be useful for screening blood products, since there is a risk that people can be carriers of prions without having any symptoms of disease.

In the UK it was discovered that 66 people had received blood from blood donors who were infected with the human form of BSE (a variant of Creutzfeldt-Jakob’s disease, vCJD), and among them, four individuals have been shown to be infected (source: Health Protection Agency, Jan. 2007).

“Using our methods, we can directly see the structure of the prions and thereby deduce the disease,” says Peter Nilsson, one of the lead authors of the article. Nilsson also developed the technique as a doctoral student at Linköping University and now, as a post-doctoral fellow with Professor Adrian Aguzzi’s research team in Zürich, has been applying the technology to prion diseases.

“For us researchers it is truly exciting to use this technique to understand more about both prions and other defectively folded proteins that give rise to similar disorders, such as Alzheimer’s,” says Peter Hammarström, co-author and research director of the prion laboratory at Linköping.


1. Christina J Sigurdson, K Peter R Nilsson, Simone Hornemann, Guiseppe Manco, Magdalini Polymenidou, Petra Schwartz, Mario Leclerc, Per Hammarström, Kurt Wüthrich, and Adriano Aguzzi. Prion strain discrimination using luminescent conjugated polymers. Nature Methods - 4, 1023-30 (2007). Published online: 18 November 2007; | doi:10.1038/nmeth1131

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