11 Scrapie, Chronic Wasting Disease, and Transmissible Mink Encephalopathy

Transmissible spongiform encephalopathies (TSE) such as scrapie in sheep and goats, transmissible mink encephalopathy (TME), and chronic wasting disease (CWD) of cervids belong to a group of diseases that affect both humans and animals, known as prion diseases. They are associated with alterations in conformation of a neural cell-surface glycoprotein, the prion protein (PrP C ) that aggregates and accumulates in the brain of affected animals or humans. This abnormal form of PrP (PrP Sc , also called PrP-res) is thought to be an essential component of the infectious particle causing TSEs, named prion (Prusiner 1982). In mice, it has been shown that TSE development is dependent on the agent strain, the infectious dose, and the host genotype (Bruce et al. 1991). Recent data now indicate that development of scrapie in sheep, CWD, and TME follows the same rules. SCRAPIE Epidemiology Sheep, goats, and moufflon ( Ovis musimon ) (Wood et al. 1992) are susceptible to natural scrapie, and the disease occurs primarily in sheep of breeding age. Scrapie is an enzootic fatal neurodegenerative disorder of unknown etiology. The disease is also called tremblante (trembling) in France, traberkrankheit in Germany (trotting disease), or rida in Iceland (ataxia or tremor). Scrapie was the first spongiform encephalopathy whose transmissibility was demonstrated (Cuille and Chelle 1936). Epidemiological studies have been conducted on the potential risk of transmission of the scrapie agent to humans but have never supported a causal relationship (Chatelain et al. 1981). Scrapie was initially reported in Europe in 1732 in England and in 1759 in Germany.

Chronic wasting disease (CWD) has recently emerged in North America as an important prion disease of captive and free-ranging cervids (species in the deer family). CWD is the only recognized transmissible spongiform encephalopathy (TSE) affecting free-ranging species. Three cervid species, mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni), are the only known natural hosts of CWD. Endemic CWD is well established in southern Wyoming and northern Colorado, and has been present in this 'core area' for two decades or more. Apparently CWD has also infected farmed cervids in numerous jurisdictions, and has probably been endemic in North America's farmed deer and elk for well over a decade. Several free-ranging foci distant to the Colorado-Wyoming core area have been discovered since 2000, and new or intensified surveillance may well identify even more foci of infection. Whether all of the identified captive and free-ranging foci are connected via a common original exposure source remains undetermined. Some of this recently observed 'spread' may be attributable to improved detection or natural movements of infected deer and elk, but more distant range extensions are more likely caused by movements of infected captive deer and elk in commerce, or by some yet unidentified exposure risk factor. Research on CWD over the last 5 years has resulted in a more complete understanding of its pathogenesis and epidemiology. CWD is infectious, transmitting horizontally from infected to susceptible cervids. Early accumulation of PrP(CWD) in alimentary tract-associated lymphoid tissues during incubation suggests agent shedding in feces or saliva as plausible transmission routes. Residual infectivity in contaminated environments also appears to be important in sustaining epidemics. Improved tests allow CWD to be reliably diagnosed long before clinical signs appear. Implications of CWD are not entirely clear at this time. Natural transmission to humans or traditional domestic livestock seems relatively unlikely, but the possibility still evokes public concerns; impacts on wildlife resources have not been determined. Consequently, where CWD is not known to occur surveillance programs and regulations that prevent or reduce the likelihood that CWD will be introduced into these jurisdictions should be encouraged. Where CWD is known to occur, affected jurisdictions are conducting surveillance to estimate and monitor trends in geographic distribution and prevalence, managing deer and elk populations in attempts to limit spread, and developing and evaluating techniques for further controlling and perhaps eradicating CWD. Programs for addressing the challenges of CWD management will require interagency cooperation, commitment of funds and personnel, and applied research. Chronic wasting disease (CWD) is perhaps the most enigmatic of the naturally occurring prion diseases. Although recognized as a transmissible spongiform encephalopathy (TSE) since the late 1970s (Williams and Young 1980, 1982), interest in and concern about CWD has only recently emerged. CWD most closely resembles scrapie in sheep in most respects, but recent media and public reaction to CWD has been more reminiscent of that afforded to bovine spongiform encephalopathy (BSE) less than a decade ago. Yet, with the exception of transmissible mink encephalopathy (TME), CWD is the rarest of the known animal TSEs: fewer than 1,000 cases have been diagnosed worldwide, and all but two of these occurred in North America. CWD is unique among the TSEs in that it affects free-living species (Spraker et al. 1997; Miller et al. 2000). The three natural host species for CWD, mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni), are all in the family Cervidae and native to North America. Like scrapie, CWD is contagious: epidemics are self-sustaining in both captive and free-ranging cervid populations (Miller et al. 1998, 2000). The geographic extent of endemic CWD in free-ranging wildlife was initially thought to be quite limited and its natural rate of expansion slow; however, recent investigations have revealed that CWD has been inadvertently spread much more widely via market-driven movements of infected, farmed elk and deer. Both the ecological and economic consequences of CWD and its spread remain to be determined; moreover, public health implications remain a question of intense interest. Here, we review current understanding of CWD, its implications, and its management.

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurological diseases that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, camel spongiform encephalopathy (CSE) in camels and chronic wasting disease (CWD) in cervids. A key event in prion diseases is the conversion of the cellular, host-encoded prion protein (PrPC) to its abnormal isoform (PrPSc) predominantly in the central nervous system of the infected host (Aguzzi et al., 2004). These diseases are transmissible under some circumstances, but unlike other transmissible disorders, prion diseases can also be caused by mutations in the host gene. The mechanism of prion spread among sheep and goats that develop natural scrapie is unknown. CWD, transmissible mink encephalopathy (TME), BSE, feline spongiform encephalopathy (FSE), and exotic ungulate encephalopathy (EUE) are all thought to occur after the consumption of prion-infected material. Most cases of human prion disease occur from unknown reasons, and greater than 20 mutations in the prion protein (PrP) gene may lead to inherited prion disease. In other instances, prion diseases are contracted by exposure to prion infectivity. These considerations raise the question of how a mere protein aggregate can bypass mucosal barriers, circumvent innate and adoptive immunity, and traverse the blood-brain barrier to give rise to brain disease. Here, we will briefly introduce a few topics in current prion studies.

Bovine spongiform encephalopathy

Transmissible spongiform encephalopathies (TSE) are sub-acute neurodegenerative disorders which include scrapie in sheep, bovine spongiform encephalopathy in cows, and Creutzfeldt-Jakob disease (CJD), kuru, Gerstmann-Straussler syndrome, and fatal familial insomnia in humans. The essential pathogenic component of TSE is an abnormal isoform of the prion protein designated PrPSc (for reviews and discussions see 1.) The naturally occurring, cellular prion protein, called PrPC, encoded by the Prnp gene, is expressed in neurons (2) and glia (3). PrPC is glycosilated and anchored to the plasma membrane, but little is known about its cellular function (see references in 1.) During the disease process, PrPC is converted into PrPSc in both neurons and astrocytes. The “converted” PrPSc is partly resistant to proteinase K digestion and has an altered conformational state whereby the amount α-helical structure decreases and the content of β-sheet increases (for review see 1). Prion-induced encephalopathies are characterized by intracerebral accumulation of PrPSc and deposition of PrP amyloid (for review see 1,4). The observation that Prnp knockout mice do not develop spontaneous scrapie (5) supports the view that the accumulation of PrPSc and PrP amyloid in the brain mediate neuronal toxicity in the central nervous system.

Transmissible spongiform encephalopathies (TSE), or prion diseases, are a family of inevitably fatal neurodegenerative disorders affecting a variety of mammalian species. These diseases include scrapie in sheep and goats; bovine spongiform encephalopathy (BSE, “mad cow” disease) in cattle; chronic wasting disease (CWD) in North American deer, elk and moose; transmissible mink encephalopathy; and Creutzfeldt-Jakob disease (CJD, sporadic, familial and variant forms) and kuru in humans. These diseases are characterized by long incubation periods, spongiform degeneration of the brain and accumulation of an abnormally folded isoform of the prion protein, designated PrPSc, in brain tissue (Prusiner 1998). CWD and scrapie are the only TSEs that appear to be environmentally transmitted. Therefore, this chapter focuses primarily on these two TSEs. Scrapie has been known in sheep for at least 250 years (McGowan 1922). Most clinically infected sheep exhibit the obvious feature of excessive rubbing and scratching of the skin; the term “scrapie” derives from this symptom. The peak incidence of scrapie occurs in sheep three to four years of age although the earliest cases are seen at 18 months and the latest in animals older than 10 years (Dickinson 1976). The origin of the scrapie agent is unknown, but a familial pattern exists in natural sheep scrapie suggesting that genetics and, possibly, vertical transmission are important. Scrapie has a world-wide distribution and has been documented wherever sheep are raised, with the exception of Australia and New Zealand. CWD was first identified at a Colorado research facility in 1967 (Williams and Young 1980) and has since been identified in captive cervid populations in Wyoming, Wisconsin, Saskatchewan, South Dakota, Oklahoma, New York, Nebraska, Montana, Minnesota, Kansas and Alberta (Fig. 1⇓). In the free-ranging cervid population, CWD has been found in Wyoming, Wisconsin, Utah, South Dakota, Saskatchewan, New Mexico, Nebraska, Illinois, …

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein-misfolding neurodegenerative diseases. TSEs have been described in several species, including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (called PrP(Sc)) in the central nervous system and other tissues, depending on the host species. Typically, TSEs are acquired through exposure to infectious material, but inherited and spontaneous TSEs also occur. All TSEs share pathologic features and infectious mechanisms but have distinct differences in transmission and epidemiology due to host factors and strain differences encoded within the structure of the misfolded prion protein. The possibility that BSE can be transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has brought attention to this family of diseases. This review is focused on the TSEs of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and goats.

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a large group of transmissible, progressive, and invariably fatal neurodegenerative conditions that affect both animals and humans (1–5). Prion diseases are unique in that they can be inherited, occur sporadically, or can be acquired by infection (1, 3–5). As described below, the infectious agent in the prion disease is composed mainly or entirely of an abnormal conformation of a host-encoded glycoprotein called the cellular prion protein (PrPC). The replication of prions involves the recruitment of the normally expressed prion protein (PrPC) structure, which is largely alpha-helical, into a disease-specific conformation (PrPSc) that is rich in beta-sheets and that can adopt a fibrillar aggregated structure that is characteristic of many of the deposits found in the brains of TSE-affected species. In contrast to the protease-sensitive PrPC, the beta-sheet conformation along with the aggregation properties of PrPSc makes this protein partially resistant to proteolytic digestion (6). Furthermore, this posttranslational modification of PrPC into the abnormal, infection-associated isoform, PrPSc, is believed to be the principal molecular basis underlying prion diseases. Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, chronic wasting disease (CWD) of cervids (predominantly mule deer and elk), transmissible mink encephalopathy (TME), feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, and spongiform encephalopathy of nonhuman primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, most animal prion diseases occur via the acquisition of infection from contaminated feed or via exposure to environmental contaminants. Scrapie and CWD are naturally sustaining epidemics. The human prion diseases can be sporadic, inherited, or acquired. Sporadic human prion diseases include Creutzfeldt-Jakob disease (sCJD), fatal insomnia, and variably protease-sensitive prionopathy (VPSPr) (3, 4). Genetic prion diseases are caused by inheritance of autosomal dominant mutations in the host PRNP gene, which encodes the normal cellular PrPC and includes genetic CJD (gCJD), fatal familial insomnia (FFI), and Gerstmann-Straussler-Scheinker syndrome (GSS) (3, 4). Acquired human prion diseases account for only 5% of cases of human prion disease. They include kuru, iatrogenic CJD (iCJD), and variant CJD (vCJD) (3, 4), which was transmitted to humans from affected cattle via meat consumption. The transmission of BSE to humans has resulted in more than 200 cases of vCJD and has raised serious public health concerns. All prion diseases have long incubation periods but are typically rapidly progressive once clinical symptoms begin. Currently, there are no effective treatments for prion diseases, although increased understanding of their pathogenesis has recently led to the promise of effective therapeutic interventions. Numerous therapeutic approaches are under development both for the prevention of prion disease prior to or shortly after exposure and for treatment of already symptomatic disease (2, 7–10).

Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. The emergence of BSE and its spread to human beings in the form of variant Creutzfeldt-Jakob disease (vCJD) resulted in interest in susceptibility of cattle to CWD, TME and scrapie. Experimental cross-species transmission of TSE agents provides valuable information for potential host ranges of known TSEs. Some interspecies transmission studies have been conducted by inoculating disease-causing prions intracerebrally (IC) rather than orally; the latter is generally effective in intraspecies transmission studies and is considered a natural route by which animals acquire TSEs. The "species barrier" concept for TSEs resulted from unsuccessful interspecies oral transmission attempts. Oral inoculation of prions mimics the natural disease pathogenesis route whereas IC inoculation is rather artificial; however, it is very efficient since it requires smaller dosage of inoculum, and typically results in higher attack rates and reduces incubation time compared to oral transmission. A species resistant to a TSE by IC inoculation would have negligible potential for successful oral transmission. To date, results indicate that cattle are susceptible to IC inoculation of scrapie, TME, and CWD but it is only when inoculated with TME do they develop spongiform lesions or clinical disease similar to BSE. Importantly, cattle are resistant to oral transmission of scrapie or CWD; susceptibility of cattle to oral transmission of TME is not yet determined.

The transmissible spongiform encephalopathy (TSE) diseases are a group of rare, fatal, and transmissible neurodegenerative diseases that include kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, transmissible mink encephalopathy (TME), and chronic wasting disease (CWD) in mule deer and elk. Over the last 20 yr, they have gone from a fascinating but relatively obscure group of diseases to one that is a major agricultural and economic problem as well as a threat to human health. The shift in the relative impact of the TSE diseases began in the late 1970s when the United Kingdom altered the process by which animal carcasses were rendered to provide a protein supplement (i.e., meat and bone meal) to sheep, cattle, and other livestock. Several years later a new disease was recognized in the British cattle population. The pathological and immunohistochemical characteristics of the disease clearly placed it among the TSEs. The new disease was named bovine spongiform encephalopathy (BSE) by the scientific community and "mad cow disease" by the less-than-scientific press. At its peak in the UK, several thousand cattle a year were diagnosed with BSE, and millions of cattle were slaughtered. Introduction of the specified offals ban as well as banning the practice of feeding ruminants to other ruminants has led to a drastic decrease in the number of yearly BSE cases in the UK (less than 500 in 2003), and the epidemic is clearly on the wane. However, BSE has now spread throughout the rest of Europe, as well as to Japan, Russia, Canada, and Israel and thus remains a worldwide problem.A primary concern following the identification of BSE in 1985 was that it might cross species barriers to infect humans. Initially, it was thought that transmission of BSE to humans was unlikely, given that humans appeared to be resistant to scrapie, an animal TSE that had been endemic in British sheep for centuries. However, a few years after BSE was first recognized, a previously unknown form of CJD (variant CJD or vCJD) was identified in young people in Great Britain. The hypothesis that vCJD was the consequence of exposure of humans to BSE has now been supported by several different studies, and over 140 cases of vCJD have been confirmed.

Prions are recognized as misfolded, pathologic isoforms of the normal mammalian prion protein, which can uniquely cause infectious inherited or spontaneous disease. They are agents of transmissible spongiform encephalopathies (TSEs). The normal, benign, host-encoded forms of PrP are denoted PrPC, and the infectious disease-associated, misfolded conformers are designated PrPTSE. Earlier it was hypothesized that TSEs were caused by a new type of “slow virus” that was too small to purify but had virus-like phenotypes such as transmissibility and heritability. This was the predominantly held theory until 1982, when Stanley Prusiner proposed that the causative agent was exclusively a protein. He solidified the “protein-only” hypothesis which had been developing and termed the agent proteinacious infectious only, or prion. Prion diseases are a family of inevitably fatal neurodegenerative disorders affecting a variety of mammalian species, including human diseases such as Creutzfeldt-Jakob disease (CJD), variant CJD (vCJD), Kuru, Fatal Familial Insomnia (FFI) and Gerstmann-Straussler-Scheinker Syndrom (GSSS). Animal prion diseases include chronic wasting disease (CWD) in North American deer, elk and moose; scrapie in sheep and goats, bovine spongiform encephalopathy (BSE: “mad cow” disease) in cattle, and transmissible mink encephalopathy (TME) in mink. These diseases are characterized by long incubation periods, spongiform degeneration of the brain and accumulation of an abnormally folded isoform of the prion protein, designated PrPSc, in brain tissue. The unusual nature of prions has created a formidable challenge for detection and study of the agent. Studies have shown prions to adsorb strongly to soil components, remain infectious and persist for years. Indirect transmission most likely occurs through incidental and geophagic ingestion of soil or other contaminated fomites, as well as deer sign-post behavior such as scraping and marking overhanging branches.

Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrP(Sc) type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

Prion diseases are a group of transmissible and fatal neurodegenerative diseases. Also known as transmissible spongiform encephalopathies (TSEs), prion diseases are associated with the host’s cellular prion protein (PrPC) misfolding into an infectious form (PrPSc). The prion protein is unique, as PrPSc can transmit from one host to another and cause disease. Many species are affected by prion diseases, including sheep with scrapie, cattle with bovine spongiform encephalopathy (BSE), cervids with chronic wasting disease (CWD), as well as humans with Creutzfeldt-Jakob disease, Kuru, Fatal Familial Insomnia, and Gerstmann-Straussler-Scheinker disease. Within these species, different strains of prion disease are thought to be encoded by different PrPSc conformations. Strains of prion disease are defined by disease phenotype, which may include disease pathogenesis, PrPSc distribution, molecular characteristics, biochemical nature, and biological properties. In the studies that make up this dissertation, we utilized strain differentiation techniques in order to characterize and categorize novel prion diseases in white-tailed deer (WTD) and cattle. The strain differentiation techniques used to compare disease phenotype include: disease pathogenesis (via experimental incubation period), PrPSc distribution (via immunohistochemistry), molecular characteristics (western blot), biochemical nature (PrPSc conformational stability), and biological properties (mouse bioassay). Our work demonstrated that a novel strain of prion disease was produced following interspecies transmission of classical sheep scrapie to white-tailed deer (WTD scrapie). Upon first passage of classical sheep scrapie in white-tailed deer, molecular differences were observed in the brainstem and cerebrum. Therefore, we oronasally inoculated region-specific WTD scrapie agents (brainstem and cerebrum) into separate groups of white-tailed deer. Upon second passage, we differentiated WTD scrapie from chronic wasting disease by the former’s PrPSc distribution (intraneuronal accumulation of PrPSc in the retinal ganglion cells), biological properties (longer survival period in cervidized transgenic mice), and biochemical nature (lower conformational stability of the misfolded prion protein). We further differentiated WTD scrapie into substrains due to the persistence of different molecular characteristics upon second passage in white-tailed deer. These substrains are termed region-specific WTD scrapie from brainstem (WTD scrapie rs-b) and region-specific WTD scrapie from cerebrum (WTD scrapie rs-c). While the PrPSc of WTD scrapie rs-b has similar N-terminal immunoreactivity compared to CWD, white-tailed deer with WTD scrapie rs-c do not. Additionally, we reported the novel presence of low-type BSE in a polymorphic (EK) bovine following intracranial inoculation. In this steer, a heritable polymorphism in the prion protein gene resulted in the replacement of glutamic acid with lysine at codon 211 of the prion protein (E211K). The EK steer with low-type BSE had a disease pathogenesis similar to wildtype (EE) low-type BSE (shorter experimental incubation period). Further, the lab-generated EK low-type BSE isolate had similar PrPSc distribution (cerebellar cortex and retinal ganglion cells), molecular characteristics (diglycosylation of PrPSc), and biological properties (shorter survival period in TgBov and K211 transgenic mice) to wildtype low-type BSE. Overall, the research presented in this dissertation provides insight into the propagation of novel prion diseases in white-tailed deer and cattle. In white-tailed deer, we define the substrains of WTD scrapie upon second passage (WTD scrapie rs-b and WTD scrapie rs-c). In both cases, the disease phenotype produced by WTD scrapie is different from CWD in white-tailed deer. Additionally, our examination of an EK steer with low-type BSE concurs with previous studies which state that the strain of BSE has a greater effect than the host genotype on disease phenotype. Together, this dissertation expands our understanding of the intersection of TSE strain, disease phenotype, and host genotype in relevant host models of prion disease.

A prion is a small infectious particle, which resist inactivation by procedures that modify nucleic acids. Transmissible spongiform encephalopathies (TSEs also known as prion diseases) are a group of progressive conditions that affects the brain and nervous system of humans and animals and are transmitted by prions. Unlike other kinds of infectious diseases that are spread by microbes, the infectious agent in TSEs is a specific protein called prion protein (PrP). TSEs are unique diseases in that they can be inherited, occur spontaneously (sporadic TSE) or can be spread through infection. The clinical signs of the disease in humans vary, but commonly include personality changes, psychiatric problems such as depression, lack of coordination and/or an unsteady gait (ataxia). Patients also may experience involuntary jerking movements called myoclonus, unusual sensation, insomnia, and confusion or memory problems. In the later stages of the disease, patients may have severe mental impairment (dementia) and may lose the ability to move or speak. Well known prion diseases include scrapie (in sheep and goat), bovine spongiform encephapathy (BSE or mad cow disease) and Creutzfeldt- Jakob disease (CJD). Less well known prion diseases include the transmissible mink encephalopathy (TME) (in mink), chronic wasting disease (CWD) (in mule, deer and elk), feline spongiform encephalopathy (FSE) (in cats), Gerstmann-Straussler-Scheinker syndrome (GSS), Alpers syndrome, and fatal familial insomnia (FFI). Six of these affect humans: CJD, GSS, FFI, mad cow disease known as (new) variant CJD, (nvCJD), Alpers syndrome and kuru. These conditions form a spectrum of diseases with overlapping signs and symptoms. There is currently no treatment that can cure or control TSEs.African Journal of Clinical and Experimental Microbiology Vol. 9 (1) 2008: pp. 38-52

Prion diseases refer to a group of invariably neurodegenerative diseases in humans and animals, collectively known as transmissible spongiform encephalopathies (TSEs). These diseases are caused by proteinaceous infectious particles that lack nucleic acid, called prions. This paper reviews prion diseases occurring in animals, excluding human spongiform encephalopathies. Prions in animals include scrapie or ovine spongiform encephalopathy, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), chronic wasting disease (CWD) of mule deer and elk, and feline spongiform encephalopathy (FSE). These diseases share several characteristics: a long incubation period (ranging from months to years or even decades), a clinical course lasting from weeks to years that invariably ends in death, lesions largely restricted to the central nervous system, and a lack of immune response. Histopathological changes include neuronal degeneration with vacuolation (spongiform degeneration), reactive astrocytosis, and often "amyloid plaque" formation. Variations exist among these diseases concerning incidence, breed and species susceptibility, and incubation time. While extensive information is available for scrapie and BSE, data on other animal spongiform encephalopathies remain limited. This paper discusses the occurrence, host range, clinical signs, histopathology, transmission, and diagnosis of these diseases, with a particular focus on scrapie and BSE. It is suggested that BSE resulted from cattle ingesting meat and bone meal from scrapie-infected sheep, and TME is considered to have originated similarly. Bovine-to-bovine transmission has been linked to feeding cattle with bovine-derived meat and bone meal. Consequently, the ban on using ruminant-derived meat and bone meal has significantly reduced the incidence of BSE. There is no direct evidence that animal spongiform encephalopathies are transmissible to humans. However, cases of a new variant of Creutzfeldt-Jakob Disease (vCJD) in teenagers and young adults in Britain and France revealed distinct neurological lesions not observed in classical CJD cases in adults from the United States, Australia, or Japan. These lesions, characterized by numerous amyloid plaques, are similar to those found in macaques inoculated with bovine prions. None of the transmissible spongiform encephalopathies discussed in this paper have been reported in the Philippines