When sprayed into the air, prions that cause mad cow and other neurodegenerative diseases may be in one of their most lethal forms.

A new study has revealed one short exposure to sprayed prions can be 100 percent lethal in mice. While the discovery doesn’t present any foreseeable public health threat, it comes as a surprise to scientists who study prion-based diseases and calls existing safety rules for laboratories and slaughterhouses into question.

"Common knowledge is that prions aren't airborne, and can't cause infection that way," said neuropathologist Adriano Aguzzi of University Hospital Zurich, co-author of a study appearing today in PLoS Pathogens. "We were totally surprised and also a bit frightened at how efficient [airborne infections] were."

Most infectious diseases are spread by bacteria or viruses, which use genes to copy themselves. But prions are a third form of disease discovered in 1982, and they're made only of misfolded proteins. The molecules resemble regular proteins found in the brain cells and other nervous tissues, but their abnormal shape converts healthy proteins into long fibrils that ultimately kill cells.

Like a chain reaction, fibrils create more prions until the host dies from destroyed brain and nervous tissue. All prion infections are 100 percent fatal, and symptoms appear suddenly months or years after infection.

"Prions are like an enemy within, the alien in some B-movie that transforms people to an evil version," said prion biologist Edward Hoover of Colorado State University, who was not involved in the study. "The immune system doesn't see them coming."

Five known human prion diseases exist, including Creutzfeldt-Jakob disease, as well as six non-human diseases, including scrapie, chronic wasting disease and mad cow disease (which sometimes jumps to humans through contaminated meat).

Although prions infect only one to two people per million in the United States each year, as much as 15 percent of deer in some Colorado populations carry chronic wasting disease. Such diseases spread via infected body fluids and tissue, yet only inconclusive evidence on airborne transmission existed until now.

To see if airborne prions could cause infection in mammals, Aguzzi and his team exposed several small groups of mice to different concentrations and exposure times of aerosolized prions that cause scrapie.

All mice except one group, which was exposed to a very light concentration of prions, got infected and died about 150 to 200 days after exposure. When it came to a lethal dose, the researchers also found that prion concentration didn't matter as much as exposure time. A group of four mice exposed for one minute to a light dose of prion-infected fluid, for example, died from scrapie in about 200 days.

Other forms of prion exposure typically require high concentrations of them to do anything, so Aguzzi said the lethality wasn't what he expected. Roughly 100,000 times more prions, for example, are required to cause an infection through the mouth compared to brain-to-brain contamination.

"That's part of the reason why we don't see more cases of prion diseases," Aguzzi said.

Because the incidence of prion disease is so low among humans – and continues to remain low – it's unlikely airborne forms are a significant threat to most people.

"I think this study is interesting and comprehensive, but my big question is this: Where do prions exist in aerosolized form?" said prion biologist Anthony Kincaid of Creighton University, who also was not involved in the research. "People who remove brains or spinal chords often use bone saws, so those might make infected tissue airborne. Otherwise I'm not sure."

Slaughterhouse environments may also be a concern, Kincaid added, but the jury is out until further research is done. Until then, he agreed with Aguzzi and Hoover that laboratory protocols are worth revising.

"My real hope in studying prions is apply what I learn to much more common but similar diseases, such as Alzheimer's," Aguzzi said. "Knowing why aggregated proteins damage neurons will allow us to understand how they affect brain function."

Image: Flickr/Darin House - MOmilkman

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