Prion最新文献

{"title":"Monte Carlo simulation of testing requirements for chronic wasting disease (CWD) surveillance via hunter-harvest in Illinois, USA.","authors":"Jameson J Mori, William M Brown, Nelda A Rivera, Daniel J Skinner, Peter E Schlichting, Jan E Novakofski, Nohra E Mateus-Pinilla","doi":"10.1080/19336896.2026.2725518","DOIUrl":"10.1080/19336896.2026.2725518","url":null,"abstract":"<p><p>Managing chronic wasting disease (CWD) - a fatal, transmissible prion disease of cervids - has many challenges, such as determining the number of cervids to test to accurately estimate true prevalence with apparent prevalence. Options range from basic equations to complex techniques like agent-based modelling, but the former does not account for parameter uncertainty, and more detailed models may be less accessible for managers. Our study used Monte Carlo simulation to create a reference table showing the number of hunter-harvested deer to test to approximate herd true prevalence with a ± 2% margin of error and 95% confidence. A three-step process was simulated in which deer from the <i>total population</i> were harvested (<i>testable subpopulation</i>), and then a subset of those harvested deer were tested for CWD (<i>tested group</i>) with diagnostic testing error, with group assignment determined by random sampling. We evaluated true prevalences ranging from 0.5-20% and <i>testable subpopulation</i> sizes up to 5,000 deer from a total population of 20,000. An example from the reference table shows that detecting a 1% true prevalence in a <i>testable subpopulation</i> of 300 deer requires testing ≥280 deer, and that the only way to accurately detect a true prevalence of 0.5% is to test 600 out of 5,000 deer. Evaluating IDNR's CWD surveillance efforts found that 16.14% of counties had adequate sample sizes in a given year and could detect true prevalences as low as 1%, showing that these guidelines are achievable.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"79-88"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal chronic wasting disease infection restricts fetal head size in white-tailed deer (<i>Odocoileus virginianus</i>).","authors":"Jameson Mori, Sara Villazan Perez-Girones, Tooba Latif, Nelda Rivera, Dan Skinner, Peter Schlichting, Jan Novakofski, Nohra Mateus-Pinilla","doi":"10.1080/19336896.2026.2635296","DOIUrl":"10.1080/19336896.2026.2635296","url":null,"abstract":"<p><p>Chronic wasting disease (CWD) is a fatal neurodegenerative prion disease of cervids that can be transmitted through direct physical contact, indirect contact with a contaminated environment, or vertical transmission. CWD is characterized by a long incubation period followed by symptoms like loss of appetite resulting from the destruction of brain tissue. While the consequences for infected animals are clear, a previous study from our laboratory showing lower body weights in the foetuses of CWD-positive female deer suggests those consequences may be intergenerational. In this study, we addressed the impact of maternal CWD infection on foetal head development (as a proxy for brain growth) in wild white-tailed deer using data from CWD management efforts in northern Illinois, U.S.A. Multivariate, multilevel, Bayesian Gamma regression found that maternal CWD infection reduced foetal head nose-occipital length and crown-jaw circumference by 6.76% and frontal-occipital length by 11.31%. These findings suggest impeded brain development in the offspring of CWD-infected female deer, which could reduce fawns' survival and success after birth and lead to a decline in population fitness over time. This study is the first to demonstrate the detrimental effects of a prion disease on foetal brain development in any animal species regardless of whether vertical transmission has occurred.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"18-30"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam of Pawel P. Liberski (1954-2025).","authors":"Beata Sikorska","doi":"10.1080/19336896.2026.2640273","DOIUrl":"https://doi.org/10.1080/19336896.2026.2640273","url":null,"abstract":"<p><p>In memoriam of Pawel P. Liberski, an enthusiastic scientist of rare intelligence, a loyal and generous friend, and a truly vivid personality.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"41-44"},"PeriodicalIF":1.6,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case report of sporadic Creutzfeldt-Jakob disease presenting with progressive opsoclonus-myoclonus-ataxia-Plus (OMAS-Plus) phenotype.","authors":"Richard Hulej, Pavol Skáčik, Dana Žáková, Monika Koprušáková-Turčanová, Milan Grofik, Egon Kurča","doi":"10.1080/19336896.2026.2729488","DOIUrl":"10.1080/19336896.2026.2729488","url":null,"abstract":"<p><strong>Background: </strong>Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive prion disorder whose heterogeneous manifestations may overlap with potentially treatable neurological conditions. We report an atypical sCJD phenotype dominated by progressive dysarthria and an opsoclonus-myoclonus-ataxia-plus (OMAS-plus) phenotype, highlighting the diagnostic pitfalls relative to treatable mimics.</p><p><strong>Case presentation: </strong>A 63-year-old man presented with progressive dysarthria and bulbar symptoms suggesting myasthenia gravis, but did not improve on pyridostigmine and progressed to right-predominant hemiataxia, acral polymyoclonus, dystonia, pyramidal signs, facial palsy, and cognitive-behavioural decline. Video-oculography showed opsoclonus, upbeat nystagmus, and abnormal saccades, raising suspicion of an immune-mediated or paraneoplastic OMAS-plus; extensive autoimmune, paraneoplastic, infectious, metabolic, and neuromuscular work-up was unrevealing, and empirical corticosteroids produced no improvement. EEG lacked periodic sharp-wave complexes and CSF 14-3-3 was negative; PRNP sequencing showed a codon 129 methionine-homozygous genotype without pathogenic mutation. Brain MRI showed cortical and basal ganglia DWI/FLAIR hyperintensities, CSF RT-QuIC was positive, and neuropathological examination, together with a type 1 PrP^Sc Western blot profile, confirmed sCJD of the MM1 subtype.</p><p><strong>Discussion: </strong>An OMAS-plus presentation may occur in sCJD and may initially direct diagnostic reasoning towards potentially treatable disorders. Rapid progression, absent support for alternative diagnoses, characteristic MRI abnormalities, and RT-QuIC positivity should prompt consideration of prion disease even when conventional supportive markers are non-diagnostic.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"89-96"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prion seeding activity in DNA extractions: implications for laboratory biosafety.","authors":"Sarah C Gresch, Tamara Morrill, Maddy Ellis-Cramer, Maria Arifin, Lexi E Frank, Jason C Bartz, Marc D Schwabenlander, Tiffany M Wolf, Gordon B Mitchell, Jiewen Guan, Peter A Larsen","doi":"10.1080/19336896.2026.2619277","DOIUrl":"10.1080/19336896.2026.2619277","url":null,"abstract":"<p><p>Infectious prions (PrP^Sc) are largely resistant to proteolytic digestion, including proteinase K (PK) digestion. While nucleic acid extracts are generally considered non-infectious from a classical microbiology context (i.e. free of intact bacteria and viruses), we investigated whether standard DNA purification methods co-purify PrP^Sc, posing an unrecognized biosafety risk. Commercial DNA extraction kits can eliminate conventional pathogens but are likely ineffective against PrP^Sc due to resistance to kit reagents and enzymatic degradation. Two laboratories, the University of Minnesota Center for Prion Research and Outreach (MNPRO) and the Canadian Food Inspection Agency (CFIA), independently tested filter-based and magnetic bead-based DNA extraction kits using tissues from chronic wasting disease (CWD)-positive and -negative white-tailed deer (WTD; <i>Odocoileus virginianus</i>), as well as prion-infected and control Syrian hamster (<i>Mesocricetus auratus</i>) brains. CFIA used two filter-based kits (one automated, one manual), while MNPRO tested two manual kits (filter- and magnetic bead-based). PrP^Sc seeding activity was measured in extracted DNA and source tissues using real-time quaking-induced conversion (RT-QuIC). MNPRO found substantial to almost perfect agreement between RT-QuIC seeding activity of DNA eluates from both extraction methods and that of the source WTD tissue homogenate. CFIA optimized RT-QuIC to a 30-hour runtime, achieving 74% sensitivity and 94% specificity in 88 archived WTD DNA samples. Both laboratories concluded that commercial DNA extraction kits do not eliminate PrP^Sc, enabling carry-over into DNA eluates. Until infectivity is resolved by animal bioassay, DNA from PrP^Sc-positive tissues should be handled under biosafety protocols appropriate for the originating prion disease, with decontamination and containment procedures.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"1-16"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/19336896.2026.2684820","DOIUrl":"10.1080/19336896.2026.2684820","url":null,"abstract":"","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"i"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding.","authors":"Guilian Xu, Amanda Lopez, Selma Brkic, Susan Fromholt, Paramita Chakrabarty, David R Borchelt","doi":"10.1080/19336896.2026.2630484","DOIUrl":"10.1080/19336896.2026.2630484","url":null,"abstract":"<p><p>Mutations in superoxide dismutase 1 (SOD1) cause paralysis in familial amyotrophic lateral sclerosis and promote its misfolding into neurotoxic aggregates. Previous studies have shown that mice expressing the ALS-causing G85R variant of SOD1 develop paralysis much faster after intraspinal injection of spinal homogenates from paralysed G85R SOD1 mice. These findings, and other studies in cell models, established the prionoid templating properties of misfolded mutant SOD1. Previously, however, we noted that the widely used Gur1-G93A SOD1 mice, which express at high levels and develop paralysis by 6 months of age, were resistant to seeding by homogenates from paralysed G93A mice. A line of G93A mice that expresses at very low levels (VLE-G93A) was responsive to seeding but at low efficiency. The poor susceptibility of G93A-SOD1 mice to seeding was not what we expected if prion-like propagation is essential to SOD1 ALS pathogenesis. In our prior studies, seeding homogenates from paralysed G93A-SOD1 mice were injected into the spine of newborn mice, leading us to question whether older G93A SOD1 mice might be more susceptible to seeding. Here, we establish that adult VLE G93A SOD1 mice (up to 12 months of age) injected intrathecally with seeding homogenates containing misfolded G93A or G85R SOD1 developed accelerated motor neuron disease efficiently. Thus, we demonstrate that both the route and age of inoculation can influence the efficiency of SOD1 seeding to induce motor neuron disease in VLE G93A-SOD1 mice. These data, together with our earlier reports, suggest that prion-like templating contributes to disease progression in SOD1-ALS.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"1-17"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic changes associated with the progression of prion disease in Syrian hamsters (<i>Mesocricetus auratus</i>).","authors":"Lexi E Frank, Nicole Flack, Christopher Faulk, Alyssa J Block, Jason C Bartz, Peter A Larsen","doi":"10.1080/19336896.2026.2710965","DOIUrl":"10.1080/19336896.2026.2710965","url":null,"abstract":"<p><p>Prion diseases are fatal neurodegenerative disorders characterized by abnormally folded prion proteins inducing misfolding of normal prion proteins, leading to neurotoxic fibrils and plaques. Epigenetic mechanisms, particularly DNA methylation, are increasingly implicated in prion-like diseases (<i>e.g</i>. Alzheimer's disease), but their role in prion pathogenesis remains unclear. To investigate, we used nanopore sequencing and RNAseq to measure genome-wide methylation and gene expression in the brains of Syrian hamsters (<i>Mesocricetus auratus</i>) experimentally infected with a hamster-adapted murine synthetic prion strain (<i>n</i> = 9) and age-matched mock-infected controls (<i>n</i> = 9) at 80, 120, and 160 days post-infection (dpi). We identified 1,586, 1,692, and 2,429 differentially methylated regions (DMRs) at 80, 120, and 160 dpi, respectively. Early- and mid-stage prion disease (80 and 120 dpi) skewed towards hypermethylation, whereas late-stage prion disease (160 dpi) skewed towards hypomethylation. Gene ontology (GO) of DMR-associated genes at 160 dpi included neuron regulation and signalling, neurodevelopment, and cellular stress pathways. We identified 178 differentially expressed genes (DEGs) at 80 dpi, 90 at 120 dpi, and 616 at 160 dpi. The majority of DEGs were downregulated at 80 dpi, and at 120 and 160 dpi, most were upregulated. Overlap in DEGs across timepoints was limited, and GO terms were related to upregulation of disease/injury response and cell death pathways in later timepoints. Overall, we found a stage-specific transcriptional shift from immune suppression to widespread immune and inflammation activation. These findings provide time-resolved data on methylation and transcriptional changes associated with impaired neuronal structure, function, and communication during disease.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"52-65"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early diagnosis of a case of Heidenhain variant of Creutzfeld-Jakob disease by cerebrospinal fluid real-time quaking-induced conversion test.","authors":"Lin Li, Rong Yan, Jiawei Wang, Yanjun Guo","doi":"10.1080/19336896.2026.2645322","DOIUrl":"10.1080/19336896.2026.2645322","url":null,"abstract":"<p><p>Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, rapidly progressive, and fatal neurodegenerative disorder caused by the accumulation of abnormal prion proteins in the central nervous system. The Heidenhain variant (HvCJD), a rare subtype of sCJD, is characterized by prominent visual symptoms at onset. Diagnosing sCJD remains challenging due to non-specific clinical presentations and the limited sensitivity and specificity of conventional tests such as magnetic resonance imaging (MRI), electroencephalography (EEG), and cerebrospinal fluid (CSF) 14-3-3 protein analysis. Recently, real-time quaking-induced conversion (RT-QuIC) has emerged as a valuable tool for improving diagnostic accuracy. We present the case of a 65-year-old man who initially experienced blurred vision and diplopia, followed by rapidly progressive dementia and dysuria. Brain MRI revealed cortical diffusion-weighted imaging (DWI) hyperintensities in the right temporo-occipital region. While his CSF 14-3-3 protein test was negative, RT-QuIC assay returned positive, leading to a final diagnosis of probable CJD. The patient died 8 weeks after diagnosis. This case highlights that HvCJD is a rare but important clinical variant in which conventional CSF 14-3-3 testing may be negative, particularly early in the disease course. In contrast, RT-QuIC demonstrates high sensitivity and specificity and can significantly aid in the early and accurate diagnosis of CJD.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"45-51"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of decay on detection of chronic wasting disease (CWD) in lymph nodes using enzyme-linked immunosorbent assay (ELISA).","authors":"Jameson Mori, Daniel Barr, Benjamin Johnson, Nelda Rivera, Peter Schlichting, Daniel Skinner, Jan Novakofski, Nohra Mateus-Pinilla","doi":"10.1080/19336896.2026.2727327","DOIUrl":"10.1080/19336896.2026.2727327","url":null,"abstract":"<p><p>Surveillance of wildlife diseases poses multiple challenges, including the availability of samples for testing and, in some situations, issues with suboptimal tissue condition. Chronic wasting disease (CWD) is a prion disease threatening the health of wild and captive cervids that is diagnosed with enzyme-linked immunosorbent assay (ELISA) and/or immunohistochemistry (IHC) of retropharyngeal lymph nodes or obex tissue. IHC uses the three-dimensional structure from fresh preserved tissues to facilitate the detection of accumulated prion proteins PrP^CWD within the tissue architecture. ELISA does not require tissue structure and uses tissue lysates to detect PrP^CWD, but its ability to detect PrP^CWD in degraded diagnostic samples is unknown. We thus examined how lymph node decomposition at 4°C and 27°C for up to 12 months affects the ability of ELISA to detect CWD prions in known CWD-positive lymph nodes from wild white-tailed deer (<i>Odocoileus virginianus</i>) in Illinois, USA. We found that prions remained detectable in 100% of the lymph nodes decayed for 12 months at both temperatures, though the detection percentage in each experimental group varied over time. Our findings are the first to demonstrate that USDA-APHIS approved ELISA assays can be used on extensively degraded lymph nodes for CWD surveillance, enabling testing of tissue in suboptimal conditions using.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"66-78"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}