Understanding Prion Diseases

Prion diseases like chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob disease (CJD) are complex and always fatal neurological diseases that people can find difficult to grasp. What separates these diseases from those caused by more common germs or agents like bacteria, viruses, and fungi is that prion diseases are caused by misfolded proteins—the prion protein—not another organism.

An Introduction to Prion Protein

Proteins are not living organisms—they are molecules made of amino acids that are used by living organisms to do many things like repair muscle, create hormones, and influence how cells work. Proteins signal to organisms and cells based on the amino acids they are made of, length, and other factors. If something about a protein (e.g., its makeup, length, shape, or orientation) is incorrect, it will not function properly.

Prion protein (PrP^C) is a protein found in the brain and other parts of the body of most mammals. While the purpose of prion protein is not quite clear, it has been linked to things like sleep regulation, memory function, neuroprotection, and copper transportation. It is an important protein that is common to many species of mammals. While the specific prion proteins are specific to each species of mammal, the genes that encode the proteins (or tell the cells how to make them) are very old, and most mammals have similar prion proteins. For example, a study of the genes that humans and 25 non-human primates use to make prion proteins found that genes were 92-99% similar between humans and all the primates in the study (Schatzl, et al. 1995).

Prion Diseases

Protein shape may seem like an unimportant detail—it is not. The shape of a protein can change how a cell functions or whether a hormone works. Misfolding proteins can happen naturally, and when they build up to a high level, they can cause diseases like Alzheimer's, CJD, and Parkinson's. Prion diseases occur when the prion protein forms incorrectly—called scrapie isoform of the prion protein (PrP^Sc).

Misfolded prions cause diseases like CJD, fatal familial insomnia, and kuru. Some prion diseases are genetic, some are randomly developed, and others are infectious. All prion diseases are fatal. According to the Centers for Disease Control and Prevention (CDC), CJD is the most common prion disease. It is a rare disease that occurs at a rate of one case per million people worldwide. It usually occurs because of a random development, but some cases are caused by genetic diseases that impact the genes that encode prion protein (see About Prion Diseases from the CDC for more information). It can also be acquired by consuming infected products (e.g., meat from infected cattle), by receiving blood or organ donations from infected people, or by interacting with medical equipment that has been used on a person with CJD.

Prion diseases can occur in other species of mammals, like sheep, deer, and cattle. As a result of the similarity of prion protein between mammals, it is possible for diseased prions to spread from individual to individual within a species and between species. When a disease goes from one species to another, this is called "crossing the species barrier"—this is something that not all diseases can do. Prion diseases that can spread are called transmissible spongiform encephalopathies (TSE) because they are a spreadable disease that makes the brain appear sponge-like. These include BSE (commonly called "mad cow"), which impacts cows; scrapie is found in sheep and goats; and CWD, which can be found in multiple species of cervids. BSE and scrapie can cross the species barrier and infect humans. At this time, it is not known if CWD can cross the species barrier.

Diseased prions become widespread in an organism through a process called seeding—a misfolded protein is introduced and that causes other prion proteins to misfold. Misfolded proteins slowly build up—aggregate—in tissue, and they cause more functioning prion to misfold, which in turn build up and cause more prion protein to misfold and aggregate. This is a chain reaction that will kill the infected organism, as misfolded prion proteins cannot perform the function of a prion protein, and groups of diseased proteins disrupt cell function. This process is often slow and can take years to manifest, depending on the infected species. The subtle nature of seeding makes it difficult to diagnose prion diseases or determine the source of the diseased proteins. In humans, prion diseases can be confused with other brain diseases like dementia or Alzheimer's.

A Real-World Example: BSE

Most cases of prion diseases in humans occur due to random developments, but there are transmissible prion diseases that are able to cross the species barrier. This type of prion disease is of great concern and is why most people have heard of prion disease. The worst TSE that happened took place in England; starting in the 1970s, cattle developed a prion disease—bovine spongiform encephalopathy (BSE). The original source of the disease is unknown, but two cases were identified in 1986. Cattle infected with BSE were unknowingly slaughtered and processed into beef for human consumption, and the byproducts, like blood, bone, and intestines from infected cows, were fed to other cattle and other livestock as a protein supplement called "meal." BSE spread rapidly in the British cattle herd due to the feeding of infected meal.

BSE was diagnosed after it had spread to many of the cattle in England; hundreds of thousands of cows had to be destroyed to prevent further spread, and the practice of feeding animal byproducts to animals was banned. At least 200 people in England and several outside of England developed a variation of Creutzfeldt-Jakob disease (vCJD) and died due to eating beef infected with BSE. These numbers are likely an underestimation, as diagnosing vCJD requires sampling part of the patient's brain or an autopsy, which is not always performed. Humans weren't the only species impacted by BSE; some domestic house cats and large cats in zoos developed a previously unknown prion disease—feline spongiform encephalopathy—and several species of exotic ungulates (including but not limited to American bison, kudu, and several species of oryx) in zoos were found to have exotic ungulate encephalopathy. It is likely that both diseases resulted from exposure to food or meal tainted with BSE.

The concern about the spread of vCJD is why people who were in England at the time of BSE cannot donate blood, breast milk, or other tissue. Not only did BSE kill 200 people and is still reducing tissue donation, but it also cost the English cattle industry billions of dollars as countries banned the importation of English beef, and forced restrictions or testing that are still ongoing. For example, the European Union banned English beef imports until 2006, and Russia did not lift its ban until 2012. This outbreak was not limited to the United Kingdom; cattle in countries like Ireland, Canada, and the USA tested positive for BSE, resulting in the destruction of cattle herds and bans on beef exports

Takeaway

Prion diseases are a serious but rare threat to the health of humans and other animals. They can develop randomly, be caused by genetic disorders, or be acquired (transmitted) between individuals of the same species or different species. They are unlike many other diseases because they are a misfolded protein and not another organism. This means that precautions taken to prevent other diseases may not work on them. They can be hard to diagnose, as they can be confused with other neurological diseases and may take years to develop.