The condition is fatal. Cases where people live up to 2.5 years have been described.

Although CJD is the most common human prion disease, it is still believed to be rare, estimated to occur in about one out of every one million people every year, however, an autopsy study published in 1989 and others suggest that between 3-13% of people diagnosed with Alzheimer's were actually misdiagnosed, and instead had CJD, not Alzheimer's. Presumably the people became infected through prion contaminated beef from cattle with subclinical atypical BSE, which has a very long incubation period. CJD usually affects people aged 45–75, most commonly appearing in people between the ages of 60–65. The exception to this is the more recently recognised 'variant' CJD (vCJD), which occurs in younger people.

CDC monitors the occurrence of CJD in the United States through periodic reviews of national mortality data. According to the CDC:

- CJD occurs worldwide at a rate of about 1 case per million population per year.

- On the basis of mortality surveillance from 1979 to 1994, the annual incidence of CJD remained stable at approximately 1 case per million people in the United States.

- In the United States, CJD deaths among people younger than 30 years of age are extremely rare (fewer than five deaths per billion per year).

- The disease is found most frequently in patients 55–65 years of age, but cases can occur in people older than 90 years and younger than 55 years of age.

- In more than 85% of cases, the duration of CJD is less than 1 year (median: four months) after onset of symptoms.

Transmissible spongiform encephalopathies (TSE) are very rare but can reach epidemic proportions. It is very hard to map the spread of the disease due to the difficulty of identifying individual strains of the prions. This means that, if animals at one farm begin to show the disease after an outbreak on a nearby farm, it is very difficult to determine whether it is the same strain affecting both herds—suggesting transmission—or if the second outbreak came from a completely different source.

Classic Creutzfeldt-Jakob disease (CJD) was discovered in 1920. It occurs sporadically over the world but is very rare. It affects about one person per million each year. Typically, the cause is unknown for these cases. It has been found to be passed on genetically in some cases. 250 patients contracted the disease through iatrogenic transmission (from use of contaminated surgical equipment). This was before equipment sterilization was required in 1976, and there have been no other iatrogenic cases since then. In order to prevent the spread of infection, the World Health Organization created a guide to tell health care workers what to do when CJD appears and how to dispose of contaminated equipment. The Centers for Disease Control and Prevention (CDC) have been keeping surveillance on CJD cases, particularly by looking at death certificate information.

Chronic wasting disease (CWD) is a prion disease found in North America in deer and elk. The first case was identified as a fatal wasting syndrome in the 1960s. It was then recognized as a transmissible spongiform encephalopathy in 1978. Surveillance studies showed the endemic of CWD in free-ranging deer and elk spread in northeastern Colorado, southeastern Wyoming and western Nebraska. It was also discovered that CWD may have been present in a proportion of free-ranging animals decades before the initial recognition. In the United States, the discovery of CWD raised concerns about the transmission of this prion disease to humans. Many apparent cases of CJD were suspected transmission of CWD, however the evidence was lacking and not convincing.

In the 1980s and 1990s, bovine spongiform encephalopathy (BSE or "mad cow disease") spread in cattle at an epidemic rate. The total estimated number of cattle infected was approximately 750,000 between 1980 and 1996. This occurred because the cattle were fed processed remains of other cattle. Then human consumption of these infected cattle caused an outbreak of the human form CJD. There was a dramatic decline in BSE when feeding bans were put in place. On May 20, 2003, the first case of BSE was confirmed in North America. The source could not be clearly identified, but researchers suspect it came from imported BSE-infected cow meat. In the United States, the USDA created safeguards to minimize the risk of BSE exposure to humans.

Variant Creutzfeldt-Jakob disease (vCJD) was discovered in 1996 in England. There is strong evidence to suggest that vCJD was caused by the same prion as bovine spongiform encephalopathy. 231 total cases of vCJD have been reported since it was first discovered. These cases have been found in a total of 12 countries with 178 in the United Kingdom, 27 in France, 5 in Spain, 4 in Ireland, 4 in the United States, 3 in the Netherlands, 3 in Italy, 2 in Portugal, 2 in Canada, and one in Japan, Saudi Arabia, and Taiwan.

This hypothesis postulates that an infectious viral agent is the cause of the disease. Evidence for this hypothesis is as follows:

Ataxia was observed to last for about 8 weeks in the affected animals. The ultimate result is death of the infected animals.

There is no cure or treatment for GSS. It can, however, be identified through genetic testing. GSS is the slowest to progress among human prion diseases. Duration of illness can range from 3 months to 13 years, with an average duration of 5 or 6 years.

GSS is one of a small number of diseases that are caused by prions, a class of pathogenic proteins highly resistant to proteases.

A change in codon 102 from proline to leucine has been found in the prion protein gene ("PRNP", on chromosome 20) of most affected individuals. Therefore, it appears this genetic change is usually required for the development of the disease.

This is a terminal condition and there is currently no specific treatment for the disease.

A slow virus is a virus, or a viruslike agent, etiologically associated with a disease, having a long incubation period of months to years and then a gradual onset of symptoms which progress slowly but irreversibly and terminate in a severe compromised state or, more commonly, death.

A slow virus disease is a disease that, after an extended period of latency, follows a slow, progressive course spanning months to years, frequently involving the central nervous system and ultimately leading to death. Examples include the Visna-Maedi virus, in the genus Lentivirus (family Retroviridae), that causes encephalitis and chronic pneumonitis in sheep, and subacute sclerosing panencephalitis which is apparently caused by the measles virus, as well as Paget's Disease of Bone (Osteitis Deformans) which is associated with paramyxoviridae, especially RSV and Rubeola (Measles).

The origin and mode of transmission of the prions causing CWD is unknown, but recent research indicates that prions can be excreted by deer and elk, and are transmitted by eating grass growing in contaminated soil. Animals born in captivity and those born in the wild have been affected with the disease. Based on epidemiology, transmission of CWD is thought to be lateral (from animal to animal). Maternal transmission may occur, although it appears to be relatively unimportant in maintaining epidemics. An infected deer's saliva is able to spread the CWD prions. Exposure between animals is associated with sharing food and water sources contaminated with CWD prions shed by diseased deer.

The disease was first identified in 1967 in a closed herd of captive mule deer in contiguous portions of northeastern Colorado. In 1980, the disease was determined to be a TSE. It was first identified in wild elk and mules in 1981 in Colorado and Wyoming, and in farmed elk in 1997.

In May 2001, CWD was also found in free-ranging deer in the southwestern corner of Nebraska (adjacent to Colorado and Wyoming) and later in additional areas in western Nebraska. The limited area of northern Colorado, southern Wyoming, and western Nebraska in which free-ranging deer, moose, and/or elk positive for CWD have been found is referred to as the endemic area. The area in 2006 has expanded to six states, including parts of eastern Utah, southwestern South Dakota, and northwestern Kansas. Also, areas not contiguous (to the endemic area) areas in central Utah and central Nebraska have been found. The limits of the affected areas are not well defined, since the disease is at a low incidence and the amount of sampling may not be adequate to detect it. In 2002, CWD was detected in wild deer in south-central Wisconsin and northern Illinois and in an isolated area of southern New Mexico. In 2005, it was found in wild white-tailed deer in New York and in Hampshire County, West Virginia. In 2008, the first confirmed case of CWD in Michigan was discovered in an infected deer on an enclosed deer-breeding facility. It is also found in the Canadian provinces of Alberta and Saskatchewan. In February 2011, the Maryland Department of Natural Resources reported the first confirmed case of the disease in that state. The affected animal was a white-tailed deer killed by a hunter.

CWD has also been diagnosed in farmed elk and deer herds in a number of states and in two Canadian provinces. The first positive farmed elk herd in the United States was detected in 1997 in South Dakota.

Since then, additional positive elk herds and farmed white-tailed deer herds have been found in South Dakota (7), Nebraska (4), Colorado (10), Oklahoma (1), Kansas (1), Minnesota (3), Montana (1), Wisconsin (6) and New York (2). As of fall of 2006, four positive elk herds in Colorado and a positive white-tailed deer herd in Wisconsin remain under state quarantine. All of the other herds have been depopulated or have been slaughtered and tested, and the quarantine has been lifted from one herd that underwent rigorous surveillance with no further evidence of disease. CWD also has been found in farmed elk in the Canadian provinces of Saskatchewan and Alberta. A retrospective study also showed mule deer exported from Denver to the Toronto Zoo in the 1980s were affected. In June 2015, the disease was detected in a male white-tailed deer on a breeding ranch in Medina County, Texas. State officials euthanized 34 deer in an effort to contain a possible outbreak.

Species that have been affected with CWD include elk, mule deer, white-tailed deer, black-tailed deer, and moose. Other ruminant species, including wild ruminants and domestic cattle, sheep, and goats, have been housed in wildlife facilities in direct or indirect contact with CWD-affected deer and elk, with no evidence of disease transmission. However, experimental transmission of CWD into other ruminants by intracranial inoculation does result in disease, suggesting only a weak molecular species barrier exists. Research is ongoing to further explore the possibility of transmission of CWD to other species.

By April 2016 CWD had been found in captive animals in South Korea; the disease arrived there with live elk that were imported for farming in the late 1990s.

Variant Creutzfeldt–Jakob disease (vCJD) or new variant Creutzfeldt–Jakob disease (nvCJD) is a transmissible spongiform encephalopathy which was identified in 1996 by the National CJD Surveillance Unit in Edinburgh, Scotland. It is always fatal and is caused by prions, which are mis-folded proteins. Over 170 cases of vCJD have been recorded in the United Kingdom, and around 30 cases in the rest of the world. The fact that the epidemiology of the disease coincided with an epidemic of bovine spongiform encephalopathy led to the hypothesis that consumption of BSE-infected beef caused the disease. It is a different disease from Sporadic and Familial Creutzfeldt–Jakob disease, though it is believed to be caused by the same pathogenic agent, a mis-folded protein, known as a prion.

Despite the consumption of contaminated beef in the UK being reckoned to be quite high, vCJD has infected a comparatively small cohort of people. One explanation for this can be found in the genetics of patients with the disease. The human PRNP protein which is subverted in prion disease can occur with either methionine or valine at amino acid 129, without any apparent difference in normal function. Of the overall Caucasian population, about 40% have two methionine-containing alleles, 10% have two valine-containing alleles, and the other 50% are heterozygous at this position. Only a single vCJD patient tested was found to be heterozygous; most of those affected had two copies of the methionine-containing form. Additionally, for unknown reasons, those affected are generally under the age of 40. It is not yet known whether those unaffected are actually immune or only have a longer incubation period until symptoms appear.

No treatment is available for affected sheep.

A test performed by sampling a small amount of lymphatic tissue from the third eyelid is now available.

In the United Kingdom, the government has put in place a National Scrapie Plan, which encourages breeding from sheep that are genetically more resistant to scrapie. This is intended to eventually reduce the incidence of the disease in the UK sheep population. Scrapie occurs in Europe and North America, but to date, Australia and New Zealand (both major sheep-producing countries) are scrapie-free.

Breeds such as Cheviot and Suffolk are more susceptible to scrapie than other breeds. Specifically, this is determined by the genes coding for the naturally occurring prion proteins. The most resistant sheep have a double set of "ARR" alleles, while sheep with the "VRQ" allele are the most susceptible. A simple blood test reveals the allele of the sheep, and many countries are actively breeding away the "VRQ" allele.

Out of fear of BSE, many European countries banned some traditional sheep or goat products made without removing the spinal cord, such as smalahove and smokie.

In 2010, a team from New York described detection of PrP even when initially present at only one part in a hundred billion (10) in brain tissue. The method combines amplification with a novel technology called surround optical fiber immunoassay and some specific antibodies against PrP. The technique allowed detection of PrP after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals' brains were analysed once any symptoms became apparent. They could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals' lives, and from uninfected animals. The results showed very clearly that PrP could be detected in the blood of animals long before the symptoms appeared. After further development and testing, this method could be of great value in surveillance as a blood- or urine-based screening test for scrapie.

Research is focused on better ways to monitor disease in the wild, live animal diagnostic tests, developing vaccines, better ways to dispose of animals who died from the disease and to decontaminate the environment, where prions can persist in soils, and better ways to monitor the food supply. Deer harvesting and management issues are intertwined.

Every infectious agent is different, but in general, slow viruses:

Additionally, the immune system seems to plays a limited role, or no role, in protection from these slow viruses. This may be in part because the host has acclimated to the virus, or more likely because the host must be immunocompromised in order for many of these slow virus infections to emerge, so the immune system is at a disadvantage from the start.

HDL1 is an unusual, autosomal dominant familial prion disease. Only described in one family, it is caused by an eight-octapeptide repeat insertion in the "PRNP" gene. More broadly, inherited prion diseases in general can mimic HD.

A ban on feeding meat and bone meal to cattle has resulted in a strong reduction in cases in countries where the disease was present. In disease-free countries, control relies on import control, feeding regulations, and surveillance measures.

In UK and US slaughterhouses, the brain, spinal cord, trigeminal ganglia, intestines, eyes, and tonsils from cattle are classified as specified risk materials, and must be disposed of appropriately.

An enhanced BSE-related feed ban is in effect in both the United States and Canada to help improve prevention and elimination of BSE.

The tests used for detecting BSE vary considerably, as do the regulations in various jurisdictions for when, and which cattle, must be tested. For instance in the EU, the cattle tested are older (30 months or older), while many cattle are slaughtered younger than that. At the opposite end of the scale, Japan tests all cattle at the time of slaughter. Tests are also difficult, as the altered prion protein has very low levels in blood or urine, and no other signal has been found. Newer tests are faster, more sensitive, and cheaper, so future figures possibly may be more comprehensive. Even so, currently the only reliable test is examination of tissues during a necropsy.

As for vCJD in humans, autopsy tests are not always done, so those figures, too, are likely to be too low, but probably by a lesser fraction. In the United Kingdom, anyone with possible vCJD symptoms must be reported to the Creutzfeldt–Jakob Disease Surveillance Unit. In the United States, the CDC has refused to impose a national requirement that physicians and hospitals report cases of the disease. Instead, the agency relies on other methods, including death certificates and urging physicians to send suspicious cases to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University in Cleveland, which is funded by the CDC.

To control potential transmission of vCJD within the United States, the American Red Cross has established strict restrictions on individuals' eligibility to donate blood. Individuals who have spent a cumulative time of 3 months or more in the United Kingdom between 1980 and 1996, or a cumulative time of 5 years or more from 1980 to present in any combination of countries in Europe, are prohibited from donating blood.

In 1961, Australian Michael Alpers conducted extensive field studies among the Fore accompanied by anthropologist Shirley Lindenbaum. Their historical research suggested the epidemic may have originated around 1900 from a single individual who lived on the edge of Fore territory and who is thought to have spontaneously developed some form of CJD. Alpers and Lindenbaum's research conclusively demonstrated that kuru spread easily and rapidly in the Fore people due to their endocannibalistic funeral practices, in which relatives consumed the bodies of the deceased to return the "life force" of the deceased to the hamlet, a Fore societal subunit. Corpses of family members were often buried for days then exhumed once the corpses were infested with maggots at which point the corpse would be dismembered and served with the maggots as a side dish.

The sexual dimorphism evident in the infection rates — kuru was eight to nine times more prevalent in women and children than in men at its peak — is because Fore men considered consuming human flesh to weaken them in times of conflict or battle, while the women and children were more apt to eat the bodies of the deceased, including the brain, where the prion particles were particularly concentrated. Also, the strong possibility exists that it was passed on to women and children more easily because they took on the task of cleaning relatives after death and may have had open sores and cuts on their hands.

Although ingestion of the prion particles can lead to the disease, a high degree of transmission occurred if the prion particles could reach the subcutaneous tissue. With elimination of cannibalism because of Australian colonial law enforcement and the local Christian missionaries' efforts, Alpers' research showed that kuru was already declining among the Fore by the mid‑1960s. However, the mean incubation period of the disease is 14 years, and 7 cases were reported with latencies of 40 years or more for those who were most genetically resilient, continuing to appear for several more decades. Sources disagree on whether the last sufferer died in 2005 or 2009.

Various studies have indicated prions (PrP) that infect sheep and goats with the fatal transmissible encephalopathy known as scrapie, are able to persist in soil for years without losing their pathogenic activity. Dissemination of prions into the environment can occur from several sources: mainly, infectious placenta or amniotic fluid of sheep and possibly environmental contamination by saliva or excrement.

Confirmatory testing for scrapie can only be achieved by applying immunohistochemistry of disease-associated prion protein (PrP) to tissues collected "post mortem", including obex (a brainstem structure), retropharyngeal lymph node and palatine tonsil. A live animal diagnostic, not confirmatory, test was approved in 2008 for immunochemistry testing on rectal biopsy-derived lymphoid tissue by USDA.

Natural transmission of scrapie in the field seems to occur via the alimentary tract in the majority of cases, and scrapie-free sheep flocks can become infected on pastures where outbreaks of scrapie had been observed before. These findings point to a sustained contagion in the environment, notably in the soil.

Prion concentration in birth fluids does not alter the infectivity of the prions. Naturally or experimentally infected does and ewes transmit the infection to the lambs, even when placentas have little PrP. PrP is shed at a higher percentage in sheep placentas (52–72%) than in goat placenta (5–10%) in study trials at the USDA Agricultural Research Service.

Detectable PrP has been reported in the feces of sheep both in the terminal and the early preclinical stages of the disease, suggesting the prions are likely to be shed into the environment throughout the course of the disease. Several sources of prions in feces could be postulated, including environmental ingestion and swallowing infected saliva; however, the most likely source is shedding from the gut-associated lymphoid tissue. Ruminant animals have specialized Peyer's patches that, throughout the length of the ileum, amount to about 100,000 follicles, and all of these could be infected and shedding prions into the lumen.

Scrapie prions have been found in the Peyer's patches of naturally infected asymptomatic lambs as young as four months of age.

In 2009, researchers at the Medical Research Council discovered a naturally occurring variant of a prion protein in a population from Papua New Guinea that confers strong resistance to kuru. In the study, which began in 1996, researchers assessed over 3,000 people from the affected and surrounding Eastern Highland populations, and identified a variation in the prion protein G127. G127 polymorphism is the result of a missense mutation, and is highly geographically restricted to regions where the kuru epidemic was the most widespread. Researchers believe that the PrnP variant occurred very recently, estimating that the most recent common ancestor lived 10 generations ago.

Of the discovery, Professor John Collinge, director of the MRC’s Prion Unit at University College London, has stated that:The findings of the study could help researchers better understand and develop treatments for other related prion diseases, such as Creutzfeldt-Jakob disease and Alzheimer’s disease.

The Huntington's disease-like syndromes (often abbreviated as HD-like or "HDL" syndromes) are a family of inherited neurodegenerative diseases that closely resemble Huntington's disease (HD) in that they typically produce a combination of chorea, cognitive decline or dementia and behavioural or psychiatric problems.

Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's – occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

Transmissible mink encephalopathy (TME) is a rare sporadic disease that affects the central nervous system of ranch-raised mink. It is classified as a transmissible spongiform encephalopathy, believed to be caused by proteins called prions. This disease is only known to affect adult mink.

Early-onset Alzheimer's disease, also called early-onset Alzheimer's, or early-onset AD, is Alzheimer's disease diagnosed before the age of 65. It is an uncommon form of Alzheimer's, accounting for only 5-10% of all Alzheimer's cases. Approximately 13% of the cases of early-onset Alzheimer's are familial Alzheimer's disease, where a genetic predisposition leads to the disease. The other incidences of early onset Alzheimer's, however, share the same traits as the 'late onset' form of Alzheimer's disease, and little is understood about how it starts.

Non-familial early onset Alzheimer's can develop in people who are in their thirties or forties, but that is extremely rare. The majority of people with early-onset Alzheimer's are in their fifties or early sixties.

Batten disease is a rare and fatal recessive neurodegenerative disorder that begins at birth.