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Overview of Prion Diseases

(Transmissible Spongiform Encephalopathies)

By

Pierluigi Gambetti

, MD, Case Western Reserve University

Last full review/revision Jun 2020| Content last modified Jun 2020
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Prion diseases are rare progressive, fatal, and currently untreatable degenerative disorders of the brain (and rarely of other organs) that result when a protein changes into an abnormal form called 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 (PrPC) changes shape (misfolds) and becomes abnormal. This abnormal prion protein is called scrapie prion protein (PrPSc), or prion. Scrapie refers to the prion disease first observed in sheep. Scrapie is so named because the sheep scrape themselves against trees, fence posts, or other structures and tear their wool off. The disease causes sheep to behave in other bizarre ways, and it is fatal.

Some of the newly formed prions resist being broken down by enzymes in the brain. Thus, they slowly accumulate. Prions also trigger other nearby PrPC to change into prions, and the process continues. When prions reach a certain number, disease results. Prions never change back into normal PrPC.

PrPC is present in all cells of the body but has a high concentration in the brain. Consequently, most prion diseases affect the nervous system predominantly or exclusively. The most common change caused by prions is the formation of tiny bubbles in brain cells, and the brain becomes filled with microscopic holes. When samples of brain tissue are viewed through the microscope, they somewhat resemble Swiss cheese or a sponge (hence, the term spongiform). After a period of time (which can vary), the affected cells cease to function and die.

Prion diseases may be

  • Sporadic: Occurring spontaneously, without any known reason (most common)

  • Familial: Occurring in families

  • Acquired: Acquired from contaminated material (uncommon)

Sporadic prion diseases

Sporadic prion diseases are the most common of all human prion diseases, accounting for 85 to 90% of all cases.

There are three types of sporadic prion disease:

Sporadic Creutzfeldt-Jakob disease is the most common type of the sporadic prion diseases. Worldwide, sporadic Creutzfeldt-Jakob disease occurs in about 1 in a million people each year.

In sporadic prion diseases, how the first prion forms is unknown. But it is suspected that an error occurs in a cell's processes (cell metabolism), and this error causes PrPC to spontaneously change its shape.

Familial prion diseases

Familial prion diseases involve a mutation in the gene for PrPC, which can be inherited. The mutation makes PrPC more likely to change into prions. More than 50 mutations exist. Each mutation typically causes a different prion disease. Familial prion diseases are inherited as an autosomal dominant disorder. That means that the mutation is not on the sex (X or Y) chromosomes and that only one gene for the disease, one from either parent, is required for the disease to develop.

There are three main groups of familial prion diseases:

Another familial prion disease has been recently discovered. It differs from other prion diseases because it causes diarrhea and affects nerves throughout the body years before symptoms of brain malfunction develop. It is described as prion disease associated with diarrhea and autonomic neuropathy.

Acquired prion diseases

Acquired prion diseases are rare. They occur

  • When people eat beef from prion-infected cattle—as is the case in variant Creutzfeldt-Jakob disease (sometimes called the human version of mad cow disease)

  • When a prion-contaminated organ or tissue is transplanted or grafted

  • When a prion-contaminated substance (such as a hormone) is given by injection

  • When brain surgery is done with prion-contaminated instruments

  • Rarely, when people receive a prion-contaminated blood transfusion

Kuru is also an acquired prion disease. It used to occur in natives of Papua New Guinea who practiced ritual cannibalism.

There are no reports of prion disease having been spread through casual contact with people who have the disease.

Prion Diseases in Animals

Prion diseases occur in sheep, goats, cattle, elk, deer, minks, and cats. These diseases are transmitted from one species to another when an animal does the following:

  • Eats an infected animal

  • Comes in contact with an infected animal's body fluids or waste

  • Comes in contact with soil contaminated by infected animals

  • Is housed with infected animals

Like people with Creutzfeldt-Jakob disease, affected animals gradually become uncoordinated and behave in abnormal ways as brain function deteriorates.

Scrapie, the prion disease in sheep, is so named because the sheep tend to scrape themselves against fence posts or other structures and tear their wool off.

In elk and deer, prion disease is called chronic wasting disease. In several western US states, Canada, and Norway, there is concern that chronic wasting disease may be transmitted to people who hunt, butcher, or eat affected animals. However, there have been no reports of chronic wasting disease or sheep scrapie causing prion disease in people. Researchers are studying whether chronic wasting disease can be transmitted to people.

Mad cow disease (bovine spongiform encephalopathy) 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 causes a form of Creutzfeldt-Jakob disease in a small percentage of people. First described in 1996, this form is called variant Creutzfeldt-Jakob disease (sometimes also called the human version of mad cow disease). Variant Creutzfeldt-Jakob disease differs in many ways from other forms of Creutzfeldt-Jakob disease:

  • It causes different changes in brain tissue (seen under a microscope).

  • The first symptoms tend to be psychiatric symptoms (such as anxiety or depression), rather than the memory loss and loss of coordination that occur in people who have other forms of Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease was very rare, even at its peak. As of February 3, 2020, there have been 178 cases in the United Kingdom, and as of December 2019, there have been 54 in other countries, for a total of 232 worldwide. In the United Kingdom, the number of new cases occurring each year peaked in 2000. Since then, the number has steadily declined. In the United States, the disease has been diagnosed in four people. All of them probably acquired the disease in a foreign country.

Treatment

  • Symptom relief and comfort measures

There is no cure for prion diseases, which are all fatal, usually within months to a few years after symptoms appear. Treatment focuses on symptom relief and comfort measures.

A number of strategies can help caregivers of people with a prion disease cope with the dementia caused by the disease (see sidebar Creating a Beneficial Environment for People With Dementia).

If possible, people who have a prion disease should establish advance directives 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.

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