Transmissible neurodegenerative diseases such as creutzfeldt-jakob disease are associated with:

Prion disease represents a group of conditions that affect the nervous system in humans and animals.

1. Introduction

In people, these conditions impair brain function, causing changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements, particularly difficulty with coordinating movements (ataxia). The signs and symptoms of prion disease typically begin in adulthood and worsen with time, leading to death within a few months to several years.

2. Frequency

3. Causes

Between 10 and 15 percent of all cases of prion disease are caused by mutations in the PRNP gene. Because they can run in families, these forms of prion disease are classified as familial. Familial prion diseases, which have overlapping signs and symptoms, include familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI).

The PRNP gene provides instructions for making a protein called prion protein (PrP). Although the precise function of this protein is unknown, researchers have proposed roles in several important processes. These include the transport of copper into cells, protection of brain cells (neurons) from injury (neuroprotection), and communication between neurons. In familial forms of prion disease, PRNP gene mutations result in the production of an abnormally shaped protein, known as PrPSc, from one copy of the gene. In a process that is not fully understood, PrPSc can attach (bind) to the normal protein (PrPC) and promote its transformation into PrPSc. The abnormal protein builds up in the brain, forming clumps that damage or destroy neurons. The loss of these cells creates microscopic sponge-like holes (vacuoles) in the brain, which leads to the signs and symptoms of prion disease.

The other 85 to 90 percent of cases of prion disease are classified as either sporadic or acquired. People with sporadic prion disease have no family history of the disease and no identified mutation in the PRNP gene. Sporadic disease occurs when PrPC spontaneously, and for unknown reasons, is transformed into PrPSc. Sporadic forms of prion disease include sporadic Creutzfeldt-Jakob disease (sCJD), sporadic fatal insomnia (sFI), and variably protease-sensitive prionopathy (VPSPr).

Acquired prion disease results from exposure to PrPSc from an outside source. For example, variant Creutzfeldt-Jakob disease (vCJD) is a type of acquired prion disease in humans that results from eating beef products containing PrPSc from cattle with prion disease. In cows, this form of the disease is known as bovine spongiform encephalopathy (BSE) or, more commonly, "mad cow disease." Another example of an acquired human prion disease is kuru, which was identified in the South Fore population in Papua New Guinea. The disorder was transmitted when individuals ate affected human tissue during cannibalistic funeral rituals.

Rarely, prion disease can be transmitted by accidental exposure to PrPSc-contaminated tissues during a medical procedure. This type of prion disease, which accounts for 1 to 2 percent of all cases, is classified as iatrogenic.

4. Inheritance

Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered PRNP gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the gene that occurs during the formation of a parent's reproductive cells (eggs or sperm) or in early embryonic development. Although such people do not have an affected parent, they can pass the genetic change to their children.

The sporadic, acquired, and iatrogenic forms of prion disease, including kuru and variant Creutzfeldt-Jakob disease, are not inherited.

5. Other Names for This Condition

Abstract

Prion diseases such as Creutzfeldt-Jakob disease in humans, scrapie in sheep, and BSE in cattle are transmissible and fatal neurodegenerative diseases. The infectious agent of these diseases has been designated as “prion”. It consists mainly and perhaps exclusively of a conformational variant of a physiological glycoprotein, the cellular prion, protein, PrPC, which is a copper-binding protein of the cell surface. In spite of the wealth of biochemical and biophysical information, the conformational transition from PrPC to PrPSc, the infectious isoform of the prion protein, is not well understood. Nerve cell loss in prion diseases may be caused by neurotoxic effects of the prion protein. Certain properties of the prion protein such as the apparent form of its glycosylation and conformational properties reflected by the preferential site of digestion with proteinase K are associated with particular phenotypes of prion disease. The appearance of a new variant of Creutzfeldt-Jakob disease in humans, which is most likely caused by the consumption of BSE-infected food in the UK, is cause for major concern particularly since there is no known effective treatment of prion diseases.

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1. Department of Neuropathology, Universität Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen e-mail: , , , , ,

   Hans A. Kretzschmar

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1. Hans A. Kretzschmar

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Kretzschmar, H. Molecular pathogenesis of prion diseases. European Archives of Psychiatry and Clinical Neurosciences 249 (Suppl 3), S56–S63 (1999). https://doi.org/10.1007/PL00014175

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• Issue Date: December 1999

• DOI: https://doi.org/10.1007/PL00014175

• Key words Prion
• Spongiform encephalopathy
• Creutzfeldt-Jakob disease
• Neurotoxicity
• Microglia

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