Prion diseases (transmissible spongiform encephalopathies) are rare degenerative diseases of the brain thought to be caused by a protein that converts to an abnormal form called a prion.

Before prions were identified, diseases such as Creutzfeldt-Jakob disease and other spongiform encephalopathies were thought to be caused by viruses. Prions are much smaller than viruses and differ from viruses, bacteria, and all living cells because they do not contain any genetic material. In prion diseases, a normal protein called cellular prion protein (PrP^c) changes shape and becomes an abnormal protein molecule called scrapie prion protein (PrP^sc)—prion. (Scrapie refers to a prion disease first observed in sheep.) The newly formed prion then converts other nearby PrP^c into prions, and the process continues. When prions reach a certain number, disease results. Prions never convert back into PrP^c.

PrP^c occurs in all cells of the body, with a high concentration in the brain. Consequently, prion diseases affect the nervous system predominantly or exclusively. When these proteins are converted into prions, they usually cause tiny bubbles to form in brain cells. Gradually, the affected cells die and the brain becomes filled with holes. When samples of brain tissue are viewed through a microscope, they somewhat resemble Swiss cheese or a sponge (hence the term "spongiform").

Prion disease may occur in families because people can inherit a mutation in the gene for PrP^c. The mutation makes PrP^c molecules more likely to convert to prions. Many different mutations exist. Each mutation generally causes different prion diseases, which, however, fit into three groups: familial Creutzfeldt-Jakob disease, fatal familial insomnia, and Gerstmann-Sträussler-Scheinker disease.

Prion diseases may occur spontaneously without any known reason. They are called sporadic and are the most common of all human prion diseases, accounting for 85 to 90% of all cases.

Prion diseases can also be acquired when prions originate from an external source, such as contaminated beef—as occurs in variant Creutzfeldt-Jakob disease (vCJD, sometimes called the human version of “mad cow disease”), implant of infected prion tissues, inoculation of prion-contaminated drugs, or use of prion-contaminated neurosurgical instruments. Other potential sources of prion disease besides cattle are elk and deer, which are affected by a prion disease called chronic wasting disease. However, no case of human prion disease has been reported from chronic wasting disease or sheep scrapie. When prions are acquired, symptoms generally develop years later. Kuru also is an acquired prion disease.

Symptoms common to most prion diseases include memory loss, confusion, loss of coordination, muscle twitches, dementia, and gait difficulty.

There is no cure for prion diseases, which are all fatal, usually within months to a few years. Treatment focuses on comfort measures and symptom relief. A number of strategies can help caregivers of people with a prion disease cope with the dementia caused by the disease (see Creating a Beneficial Environment for People With Dementia). If possible, people who have a prion disease should establish advance directives (see Legal and Ethical Issues: Overview of Legal and Ethical Issues in Health Care) about what kind of medical care they want at the end of life. Family members of people who develop the hereditary form of the disease may benefit from genetic counseling.

Of Sheep and Cows
Prion diseases occur in sheep, goats, cattle, and other animals, such as minks, elk, deer, and goats. Like people with Creutzfeldt-Jakob disease, affected animals gradually become uncoordinated, then develop dementia. Scrapie, the disease in sheep, is so named because the sheep tend to scrape themselves against fence posts or other objects and tear their wool off. Mad cow disease is so named because the cattle become noticeably agitated. The disease can be transmitted from sheep to cattle by feeding cattle scrapie-infected sheep parts. Eating contaminated beef or beef products is thought to be the cause of a new form of Creutzfeldt-Jakob disease in people. First described in 1996, this form is called variant Creutzfeldt-Jakob disease (sometimes also called the human version of “mad cow disease”). The new form differs in many ways from the usual form: It causes different changes in brain tissue (seen under a microscope), and the first symptoms tend to be psychiatric symptoms, rather than the memory loss that occurs in people who have the usual form of Creutzfeldt-Jakob disease. By early 2007, variant Creutzfeldt-Jakob disease had been diagnosed in a total of 201 people: 165 in the United Kingdom 21 in France 4 in Ireland 3 in the United States (2 acquired in the United Kingdom, 1 in Saudi Arabia) 2 in Holland 1 in Italy 1 in Japan (acquired in the United Kingdom) 1 in Canada (acquired in the United Kingdom) 1 in Spain 1 in Portugal 1 in Saudi Arabia

Last full review/revision January 2007 by Pierluigi Gambetti, MD