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Simple Summary: Scrapie is a neurodegenerative disease that affects sheep and goats. This study aimed to estimate the prevalence of caprine PRNP genetic variability in goat populations across the United States. The homozygous 146NN, 211RR, and 222QQ alleles, which are associated with scrapie susceptibility, were found to be the most prevalent among caprine PRNP alleles. The prevalence of different genotypes varied across regions. The 222QK allele was most frequently found in the east and southwest regions, whereas 211RQ was more common in the Midwest and east regions. The 146NS genotype had the highest prevalence in the northwest and southwest regions. These findings provide insights into the prevalence of caprine PRNP genetic variability in the United States and its potential application for scrapie susceptibility management strategies. Scrapie is a neurodegenerative disease that impacts sheep and goats, characterized by gradual and progressive changes in neurological function. Recent research shows that the scrapie incubation period is significantly influenced by specific variations in amino acids within the prion protein gene (PRNP). The objective of this study was to estimate the national prevalence of caprine PRNP genetic variability at codons 146, 211, and 222 in goat populations across the United States. A total of 3052 blood, ear tissue, and brain tissue samples were collected from goats from 50 states. The participating states were categorized into four Veterinary Service (VS) district regions. The samples underwent DNA extraction, and the PRNP variants corresponding to codons 146, 211, and 222 were amplified and sequenced. The analysis of PRNP variants, when compared to the PRNP reference sequence, revealed seven alleles in twelve genotypes. The homozygous 146NN, 211RR, and 222QQ alleles, which have been linked to an increased risk of scrapie, were found to be the most prevalent among all the goats. The heterozygous 222QK, 211RQ, 146SD, 146ND, and 146NS alleles and the homozygous 222KK, 146SS, and 146DD alleles, known to be associated with reduced scrapie susceptibility and a prolonged incubation period after experimental challenge, were found in 1.098% (222QK), 2.33% (211RQ), 0.58% (146SD), 3.13% (146ND), 20.68% (146NS), 0.005% (222KK), 3.31% (146SS), and 0.67% (146DD) of goats, respectively. The 222QK allele was found most frequently in goats tested from the east (VS District 1, 1.59%) and southwest (VS District 4, 1.08%) regions, whereas the 211RQ allele was found most often in goats tested from the Midwest (VS District 2, 8.03%) and east (VS District 1, 6.53%) regions. The 146NS allele was found most frequently in goats tested from the northwest (VS District 3, 29.02%) and southwest (VS District 4, 20.69%) regions. Our results showed that the prevalence of less susceptible genotypes at PRNP codon 146 may be sufficient to use genetic susceptibility testing in some herds. This may reduce the number of goats removed as part of a herd clean-up plan and may promote the selective breeding goats for less susceptible alleles in high-risk herds at the national level. [ABSTRACT FROM AUTHOR]

Chronic wasting disease (CWD) is a fatal prion disease of the family Cervidae that circulates in both wild and captive cervid populations. This disease threatens the health and economic viability of the captive cervid industry, which raises cervids in contained spaces for purposes such as hunting and breeding. Given the high transmissibility and long incubation period of CWD, the introduction and propagation of the infectious prion protein within and between captive cervid farms could be devastating to individual facilities and to the industry as a whole. Despite this risk, there does not yet exist a literature review that summarizes the scientific knowledge, to date, about CWD spread, surveillance, or control measures. Our review, which focused on peer reviewed, primary research conducted in the United States, sought to address this need by searching Google Scholar, Scopus, and Web of Science with a five-term keyword string containing terms related to the (1) location, (2) species affected, (3) disease, (4) captive cervid industry, and (5) topic of focus. Between the three databases, there were 190 articles that were selected for further examination. Those articles were then read to determine if they were about CWD spread, surveillance, and/or control in captive cervid facilities. The 22 articles that met these inclusion criteria were evaluated in detail and discussed, with recommendations for future collaborative work between captive cervid owners, government agencies, and researchers. This work will help to address, inform, and mitigate the rising problem of CWD spread and establishment.

Background: The United States control program for classical ovine scrapie is based in part on the finding that infection is typically spread through exposure to shed placentas from infected ewes. Transmission from goats to sheep is less well described. A suitable rodent model for examining the effect of caprine scrapie isolates in the ovine host will be useful in the ovine scrapie eradication effort. In this study, we describe the incubation time, brain lesion profile, glycoform pattern and PrPSc distribution patterns in a well characterized transgenic mouse line (Tg338) expressing the ovine VRQ prion allele, following inoculation with brain from scrapie infected goats. Results: First passage incubation times of caprine tissue in Tg338 ovinized mice varied widely but second passage intervals were shorter and consistent. Vacuolation profiles, glycoform patterns and paraffin-embedded tissue blots from terminally ill second passage mice derived from sheep or goat inocula were similar. Proteinase K digestion products of murine tissue were slightly smaller than the original ruminant inocula, a finding consistent with passage of several ovine strains in previous reports. Conclusions: These findings demonstrate that Tg338 mice propagate prions of caprine origin and provide a suitable baseline for examination of samples identified in the expanded US caprine scrapie surveillance program. [ABSTRACT FROM AUTHOR]

Dietary consumption of fish is widely recommended because of the beneficial effects of omega-3 polyunsaturated fatty acids on the risks of cardiovascular and Alzheimer's diseases. The American Heart Association currently recommends eating at least two servings of fish per week. We are concerned that consumption of farmed fish may provide a means of transmission of infectious prions from cows with bovine spongiform encephalopathy to humans, causing variant Creutzfeldt Jakob disease. [ABSTRACT FROM AUTHOR]

Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of domestic and wild cervids in North America. To address possible prevention regimens for CWD, we have used a mouse model system and the Rocky Mountain Laboratory (RML) mouse-adapted scrapie prion strain to screen efficacy of potential vaccine candidates. Three peptides derived from the primary amino acid sequence of the prion protein were conjugated to blue carrier protein (BCP) and formulated in an adjuvant containing M. avium subsp. avium. CL57/BL6 mice were vaccinated and boosted with 50μg of the carrier protein–peptide conjugate formulation; all vaccines produced a humoral immune response as measured by ELISA. Disease challenge with the RML scrapie prion strain revealed anti-prion activity was generated by the vaccine formulations as measured by a delay in clinical disease onset and prolonged survivorship. [Copyright &y& Elsevier]

The spread of chronic wasting disease (CWD) during the last six decades has resulted in cervid populations of North America where CWD has become enzootic. This insidious disease has also been reported in wild and captive cervids from other continents, threatening ecosystems, livestock and public health. These CWD "hot zones" are particularly complex given the interplay between cervid PRNP genetics, the infection biology, the strain diversity of infectious prions and the long-term environmental persistence of infectivity, which hinder eradication efforts. Here, we review different aspects of CWD including transmission mechanisms, pathogenesis, epidemiology and assessment of interspecies infection. Further understanding of these aspects could help identify "control points" that could help reduce exposure for humans and livestock and decrease CWD spread between cervids., (© 2021. The Author(s).)

The recent Research Framework proposed by the US National Institute on Aging and the Alzheimer's Association (NIA-AA) recommends that Alzheimer's disease be defined by its specific biology rather than by non-specific neurodegenerative and syndromal features. By affirming markers of abnormal Aβ and tau proteins as the essential pathobiological signature of Alzheimer's disease, the Framework tacitly reinforces the amyloid (Aβ) cascade as the leading theory of Alzheimer pathogenesis. In light of recent evidence that the cascade is driven by the misfolding and templated aggregation of Aβ and tau, we believe that an empirically grounded Standard Model of Alzheimer's pathogenesis is within reach. A Standard Model can clarify and consolidate existing information, contextualize risk factors and the complex disease phenotype, identify testable hypotheses for future research, and pave the most direct path to effective prevention and treatment.