Creutzfeldt-Jakob Disease (CJD) Frequently Asked Questions
Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a family of invariably fatal neurodegenerative disorders that affect humans and animals and are caused by prions. It is sometimes called a “spongiform” disease because the brain may develop holes like a sponge. Prions are the abnormal form of a specific normal cellular protein called a prion protein and they are found most abundantly in the brain. Prions are transmissible in certain circumstances, and they can induce abnormal folding of other normal prion proteins.
Creutzfeldt-Jakob Disease (CJD) is a human prion disease and there are several forms including sporadic, genetic, and acquired, such as iatrogenic and variant CJD. CJD usually occurs in people over the age of 60. Sporadic CJD (sCJD) occurs spontaneously and is the most common type of CJD in the United States accounting for ~85% of cases. Genetic CJD (gCJD) is inherited through a genetic mutation and is ~5-15% of cases worldwide and ~10% of cases in the United States. Iatrogenic CJD (iCJD) is acquired through contamination of neurosurgical instruments or stereotactic depth electrodes, corneal transplants, dura mater grafts, or by administration of contaminated pituitary hormones, and is very rare (<1% of all cases). Every year about one to two persons out of every million is diagnosed with CJD; most cases are sporadic CJD.
There is no known treatment, and most patients succumb to their illness within 3 to 12 months of onset of symptoms. Variant CJD (vCJD) is associated with eating a product containing contaminated tissue from cattle with bovine spongiform encephalopathy (BSE or “mad cow disease”) or from a contaminated blood or plasma transfusion. vCJD is very rare; only 4 cases have been identified in the United States between 2001-2014. All 4 cases were born overseas and there is strong evidence that exposure occurred prior to moving to the United States.
Other human prion diseases include Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI), which are specific genetic prion diseases, and Kuru, which is an acquired form of prion disease and most likely extinct.
At first, CJD can seem like other diseases of the elderly. Symptoms can vary widely and can begin in a variety of ways, but can include dementia, which is difficulty with concentrating, memory or thinking, as well as behavioral changes, mood changes, or changes in sleeping patterns. Patients may lose their balance or seem uncoordinated; they may have difficulty walking or have muscle jerks and spasms. Some patients may have issues with their vision.
The current theory for the development of CJD is that an abnormal prion protein converts a normal prion protein to the abnormal form, leading to accumulation of abnormal prion proteins that are hard to break down and destruction of brain tissue. This process gives brain tissue a sponge-like appearance under the microscope. The initial change of a normal prion protein to an abnormal prion protein is a yet uncharacterized conformational change.
Most cases of CJD are sporadic CJD, and it is not known how most people develop this rare disease, but there is no evidence of human-to-human transmission and it is thought to be due to spontaneous misfolding of a normal prion protein. Approximately 5–15% of cases are inherited (genetic CJD), and a small percentage (<1%) have been related to transplants of contaminated tissues, exposure to contaminated neurosurgical instruments or other instruments, or exposure to contaminated pituitary hormones (iatrogenic CJD).
In 1995, the first case of vCJD was recognized in the United Kingdom and has been linked to ingestion of prion contaminated beef products from cattle infected with bovine spongiform encephalopathy (BSE) (also known as “mad cow disease”) or receiving a transfusion of contaminated blood or plasma. There are also several investigations of cases with possible exposures to BSE in a laboratory.
Yes, there are multiple tests that are available. To confirm CJD, brain tissue must be examined, which can be done after an autopsy, or a brain biopsy, though brain biopsies cannot rule out CJD and are only recommended if a doctor is trying to exclude an alternative treatable disease. The National Prion Disease Pathology Surveillance Center (NPDPSC) provides free autopsy arrangement and tissue examination.
When a doctor is evaluating a patient with symptoms of CJD, other special testing is available. This testing includes cerebrospinal fluid (CSF) tests for 14–3–3 protein, total Tau protein, or RT-QuIC, and blood tests for genetic mutation testing. CSF and genetic blood testing are available at the National Prion Disease Pathology Surveillance Center. A brain MRI can be performed and may show changes that are suggestive of CJD. An EEG (or electroencephalogram), which measures electrical activity in the brain and records brain wave patterns, can also be helpful with the diagnosis
Bovine spongiform encephalopathy (BSE) or “mad cow disease” is a prion disease in cattle that causes progressive neurological disease. There are different forms of BSE, and they are categorized as “classical” (C-type) or “atypical” (L-type or H-type). Classical BSE is thought to be responsible for the BSE outbreak in the United Kingdom in the 1980s-1990s and has been reported in at least 25 other countries. The number of classical BSE cases worldwide is estimated to be extremely low (close to zero cases per year). The primary source of infection for classical BSE is feed contaminated with the infectious prion agent, such as meat-and-bone meal containing protein derived from rendered infected cattle. Regulations from the Food and Drug Administration (FDA) have prohibited the inclusion of mammalian protein in feed for cattle and other ruminants since 1997 and have also prohibited high risk tissue materials in all animal feed since 2009. The incubation period for classical BSE on average is 3-6 years. Classical BSE has not been identified in any U.S.-born cattle. The atypical BSE forms, L-type and H-type, appear to occur spontaneously at very low levels in all cattle populations, particularly in older cattle, and do not seem to be associated with contaminated feed. Bioassay data seems to indicate that these strains are biologically distinct from classical BSE and are more like sporadic CJD in humans as they are rare and spontaneous.
Per the United States Department of Agriculture (USDA), to date, there have been seven cases of BSE identified in cattle in the United States. The first case of BSE was a classical BSE case identified in a Washington State dairy cow in 2003 that was imported from Canada (non-U.S. born). The subsequent six US cases were confirmed atypical BSE in native US-born cattle. In 2005, the second reported case of BSE was identified in a 12-year-old Texas beef cow representing the first native born case in the United States. In 2006, the third case was reported in a 10-year-old Alabama beef cow. In 2012, the fourth case of BSE was reported in a 10-year-old California dairy cow. In 2017, the fifth reported case was an 11-year-old Alabama beef cow. In 2018, the sixth reported case was a 6-year-old Florida beef cow. In 2023, the seventh reported case was a 5+ year-old Tennessee beef cow that was identified in South Carolina.
In Canada, 17 of the 20 BSE cases have been associated with the classical form of BSE that is linked to vCJD in humans.
Yes, there have been four cases of variant CJD (vCJD) identified in humans in the United States. However, there is strong evidence to suggest the first and second case were exposed in the United Kingdom while residing in the United Kingdom during the defined period of risk (1980–1996), the third case was exposed in Saudi Arabia, and the fourth case is less clear as to which overseas country the exposure occurred. Additional information about each case is below.
First case - The patient was born in the United Kingdom in the late1970s and lived there until relocating to Florida in 1992. Onset of symptoms began in 2001 and the patient died in 2004.
Second case – The patient was born and raised in the United Kingdom before moving to Texas in 2001. Symptoms began in 2005, and the patient then returned to the United Kingdom. The case was confirmed neuropathologically (by autopsy) in 2006 by experts in the United Kingdom.
Third case – The patient was born and raised in Saudi Arabia and resided in the United States since 2005. Symptoms began in 2006, and variant CJD was pathologically confirmed by analysis of brain biopsy and adenoid tissue in 2006. Investigators believe that exposure most likely occurred from consumption of contaminated beef products as a child while residing in Saudi Arabia.
Fourth case – The Texas Department of State Health Services (DSHS), in conjunction with the CDC, completed the investigation of the fourth vCJD case in the United States. Symptoms began in 2012, and the patient died 18 months later. The investigation confirmed the individual was born outside the United States and indicated exposure to the BSE agent most likely occurred before moving to the United States. The individual previously resided in Lebanon, Kuwait, and Russia. The investigation did not support frequent travel or travel of any significant duration to European countries or Saudi Arabia. In absence of a definitive travel link to a country where other known vCJD cases were likely infected, it is less clear as to which specific overseas country the individual’s exposure occurred. The neuropathological analysis performed by the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University (https://case.edu/medicine/pathology/divisions/prion-center) confirmed the clinical diagnosis of vCJD.
For additional information, please visit the CDC’s vCJD Cases Reported in the US website.
Yes, other animal prion diseases are being monitored by multiple federal and state agencies in the United States. This includes BSE (see above), scrapie in sheep and goats, and chronic wasting disease (CWD) in cervids.
Scrapie, per the United States Department of Agriculture (USDA) and the National Institutes of Health (NIH), is the oldest transmissible spongiform encephalopathy and was first recognized almost 300 years ago. After extensive research, and under natural conditions, only sheep and goats are known to be affected by scrapie, and to date, there is no scientific evidence that scrapie can infect humans. In Texas, the Texas Animal Health Commission and USDA monitor scrapie.
CWD was first recognized in captive deer in a Colorado research facility in 1967 and later in 1981 in free-ranging deer. CWD has been found in more than half of US states and several Canadian provinces, as well as in Norway, Finland, Sweden, and a small number of imported cases have been reported in South Korea. CWD has been found in multiple types of cervids, including deer, elk, moose, reindeer/caribou and other cervids. CWD was first identified in Texas in 2012. In Texas, CWD is being monitored by the Texas Parks and Wildlife Department and the Texas Animal Health Commission, and USDA operates a national voluntary CWD herd certification program for farmed deer and elk. To date, there is no indication of a documented transmission of CWD to a human, and it is not known if humans can be infected with CWD prions. There have been several macaque transmission studies that had conflicting results, and the reason for the differing results is unknown. However, the World Health Organization recommends that agents of prion diseases not enter the human food chain. CDC also recommends that hunters that are hunting in areas with CWD strongly consider having animals tested before eating the meat, and generally recommends not handling or eating meat from animals that look sick, are acting strangely, or are found dead. Please see the CWD section of the Resources tab for links to additional recommendations for hunters. Studies are ongoing to collect information that could help determine if any prion diseases could be occurring at a higher rate in people who are at increased risk for contact with potentially CWD-infected deer or elk. Because of the long time it could take before any symptoms of disease appear, scientists expect studies to take many years before they will determine what the risk, if any, of CWD is to people.