Surveillance of amyloid A deposits in commercial beef liver and assessment of food hygiene risks
Susumu IWAIDE1,2)*, Natsumi KOBAYASHI2), Kenta OWAKU2) , Niki SEDGHI MASOUD2), Naoki UJIKE2), Yoshiyuki ITOH3), Takuma KOZONO3) , Miki HISADA3), Kumiko KIMURA1), Tomoyuki SHIBAHARA1,4) , Tomoaki MURAKAMI2) 1)National Institute of Animal Health, National Agriculture and Food Research Organization, Ibaraki, Japan 2)Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and Technology, Tokyo, Japan 3)Smart-Core-Facility Promotion Organization, Tokyo University of Agriculture and Technology, Tokyo, Japan 4)Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University, Osaka, Japan J Vet Med Sci 87(8): 887–893, 2025 doi: 10.1292/jvms.25-0177 Received: 7 April 2025 Accepted: 30 May 2025 Advanced Epub: 12 June 2025
ABSTRACT.
Bovine amyloid A (AA) amyloidosis has been reported to be experimentally transmitted to mice, like prion disease. Although the prevalence of AA amyloidosis in cattle at slaughterhouses has been reported in several studies, how much bovine AA is distributed in retail stores remains unknown. In this study, to clarify the food hygienic risk of bovine AA, we collected beef livers from seven commercial retail stores in Japan to investigate the deposition rate and the transmissibility of bovine AA. Congo red staining and immunohistochemistry revealed bovine AA deposition in two of 185 commercial beef livers (1.08%). No differences were observed between the gross appearance of amyloid-laden and amyloid-free livers. Administration of bovine AA from commercial beef liver to mice, either intraperitoneally or into the spleen, did not promote the development of AA amyloidosis. This contrasts with previous studies demonstrating cross-species transmission of AA amyloidosis via intraperitoneal or even oral administration of bovine AA. Although the cause of this discrepancy is unknown, the low transmissibility may be related to the species-barrier. These results support that the actual food hygienic risk of AA amyloidosis associated with consuming commercial beef liver may not be significant. KEYWORDS: amyloid A amyloidosis, cattle, cross-species transmission, food hygiene, liver
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In humans and animals that have consumed prion-contaminated food, exogenous abnormal prion protein serves as a template for amplification, resulting in an increase in amyloid fibrils and the development of prion disease [21]. In AA amyloidosis, as in prion diseases, exogenous amyloid acts as a nucleus for fibril elongation, resulting in the propagation of AA amyloidosis [14]. AA amyloidosis is promoted not only by intravenous administration of exogenous amyloid but also by intraperitoneal or oral administration [3, 5, 11, 14]. Transmission of AA amyloidosis also occurs when AA fibrils of heterologous animal origin, such as cattle, are orally administered to mice [2, 3]. These data suggest that meat-derived amyloids may cross-seed in the body of consumers and promote amyloid fibril formation [36]. So far, studies have reported that AA is deposited at a certain frequency in cattle [22, 31, 38] and chickens [6] at slaughterhouses and in commercial foie gras [28]. These findings raise concerns about the food hygienic risk of AA amyloidosis based on prion-like transmission when humans consume AA of animal origin. While one surveillance of amyloid deposition in commercial chicken liver has been reported [6], there have been no reports on amyloid deposition in commercial beef, including liver. In this study, we conducted a surveillance for AA deposition in commercially available beef liver in Japan to clarify the food hygienic risk of consuming meat-derived AA. As a result, AA deposition was found in two out of 185 commercial beef livers. Therefore, experimental transmission of amyloid fibrils from one of the commercial livers to mice was performed and its transmissibility was evaluated.
https://www.jstage.jst.go.jp/article/jvms/87/8/87_25-0177/_pdf/-char/en
Front. Aging Neurosci., 31 January 2022 | https://doi.org/10.3389/fnagi.2021.815361
Aged Cattle Brain Displays Alzheimer's Disease-Like Pathology and Promotes Brain Amyloidosis in a Transgenic Animal Model
Ines Moreno-Gonzalez1,2,3,4*, George Edwards III1, Rodrigo Morales1,4, Claudia Duran-Aniotz1,5,6, Gabriel Escobedo Jr.1, Mercedes Marquez7, Marti Pumarola7,8 and Claudio Soto1*
1Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Health Science Center at Houston, Houston, TX, United States
2Departamento Biología Celular, Genética y Fisiología, Instituto de Investigacion Biomedica de Malaga-IBIMA, Universidad de Malaga, Malaga, Spain
3Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
4Centro Integrativo de Biologia y Quimica Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile
5Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibáñez, Santiago, Chile
6Latin American Institute for Brain Health (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile
7Department of Animal Medicine and Surgery, Veterinary Faculty, Animal Tissue Bank of Catalunya (BTAC), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Valles), Barcelona, Spain
8Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Universitat Autonoma de Barcelona, Bellaterra (Cerdanyola del Valles), Barcelona, Spain
Alzheimer's disease (AD) is one of the leading causes of dementia in late life. Although the cause of AD neurodegenerative changes is not fully understood, extensive evidence suggests that the misfolding, aggregation and cerebral accumulation of amyloid beta (Aβ) and tau proteins are hallmark events. Recent reports have shown that protein misfolding and aggregation can be induced by administration of small quantities of preformed aggregates, following a similar principle by which prion diseases can be transmitted by infection. In the past few years, many of the typical properties that characterize prions as infectious agents were also shown in Aβ aggregates. Interestingly, prion diseases affect not only humans, but also various species of mammals, and it has been demonstrated that infectious prions present in animal tissues, particularly cattle affected by bovine spongiform encephalopathy (BSE), can infect humans. It has been reported that protein deposits resembling Aβ amyloid plaques are present in the brain of several aged non-human mammals, including monkeys, bears, dogs, and cheetahs. In this study, we investigated the presence of Aβ aggregates in the brain of aged cattle, their similarities with the protein deposits observed in AD patients, and their capability to promote AD pathological features when intracerebrally inoculated into transgenic animal models of AD. Our data show that aged cattle can develop AD-like neuropathological abnormalities, including amyloid plaques, as studied histologically. Importantly, cow-derived aggregates accelerate Aβ amyloid deposition in the brain of AD transgenic animals. Surprisingly, the rate of induction produced by administration of the cattle material was substantially higher than induction produced by injection of similar amounts of human AD material. Our findings demonstrate that cows develop seeding-competent Aβ aggregates, similarly as observed in AD patients.
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The prion-like transmission of Aβ aggregates has been extensively reported in animal models and likely plays an important role in the progressive spreading of pathological abnormalities throughout the brain (Moreno-Gonzalez and Soto, 2011; Thal et al., 2014; Walker and Jucker, 2015). Nevertheless, whether this phenomenon ever operates in the inter-individual transmission of disease pathology in humans remains highly debatable. Recent studies have provided evidence for the induction of Aβ aggregation in people receiving human pituitary-derived growth hormone (Jaunmuktane et al., 2015; Ritchie et al., 2017). However, when the risk of AD development, and not only amyloid pathology, was studied no evidence was found for disease transmission (Irwin et al., 2013). The findings of our current study suggest that Aβ aggregates present in the brains of old cattle are competent to seed amyloid deposition in vivo. This induction has also been observed with other protein aggregates such as AA amyloid (Rising et al., 2021). However, the potential transmission of Aβ cattle-derived seeds to humans is unlikely, considering that repeated oral administration of AD brain extracts to susceptible mice failed to accelerate pathological features (Morales et al., 2021). The results presented in this manuscript suggest that aged cattle are susceptible to develop pathological features similar to AD, and that misfolded Aβ present in their brain is seeding competent.
https://www.frontiersin.org/articles/10.3389/fnagi.2021.815361/full
P1-187 AGED CATTLE BRAIN DISPLAYSALZHEIMER’S-LIKE PATHOLOGY THATCAN BE PROPAGATED IN A PRION-LIKE MANNER
Ines Moreno-Gonzalez1, George A. Edwards, III,1, Nazaret Gamez Ruiz1,Priyadarshini Peter1, Rodrigo Morales1, Mercedes Marquez2, Marti Pumarola2,Claudio Soto1,1The University of Texas Health Science Center at Houston, Houston, TX, USA;2Animal Tissue Bank of Catalunya (BT A C), Universidad Autonoma de Barcelona, Barcelona, Spain . Contact e-mail: Ines.M.Gonzalez@uth.tmc.edu
Background: Amyloid beta (Ab) and hyperphosphorylated tau(ptau) are the proteins undergoing misfolding in Alzheimer’s dis-ease (AD). Recent studies have shown that brain homogenates rich in amyloid aggregates are able to seed the misfolding and ag-gregation of amyloidogenic proteins inducing an earlier onset of the disease in mouse models of AD. This seeding behavior is analogous to the disease transmission by propagation of prion protein misfold-ing observed in prion diseases. Prion diseases can be transmitted across species by inoculation of the misfolded prion protein from one specie into an appropriate host. For example, material from cattle affected by bovine spongiform encephalopathy can be propagate in humans inducing variant Creutzfeldt-Jakob disease.
Methods: In this study, we analyzed the presence of AD-related protein aggre-gates in the brain of old cows and investigated whether these aggregates are capable to induce pathology in animal models of AD.
Results: We observed that many of the typical hallmarks detected in human AD brains, including Ab aggregates and tangles, were present in cow brains. When cattle tissue containing Ab aggregates or ptau were intracerebrally inoculated into APP/PS1 or P301Smice, we observed an acceleration of brain misfolded protein deposition and faster cognitive impairment compared to controls. How-ever, when the material was orally inoculated, no effect was observed.
Conclusions: These results may contribute to uncover a previously unsuspected etiology surrounding some cases of spo-radic AD. However, the early and controversial stage of the field of prion-like transmission in non-prion diseases added to the artificial nature of the animal models utilized for these studies, indicate that extrapolation of the results to humans should not be done without further experiments.
https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1016/j.jalz.2018.06.191
P75 Determining transmissibility and proteome changes associated with abnormal bovine prionopathy
Dudas S (1,2), Seuberlich T (3), Czub S (1,2)
In prion diseases, it is believed that altered protein conformation encodes for different pathogenic strains. Currently 3 different strains of bovine spongiform encephalopathy (BSE) are confirmed. Diagnostic tests for BSE are able to identify animals infected with all 3 strains, however, several diagnostic laboratories have reported samples with inconclusive results which are challenging to classify. It was suggested that these may be novel strains of BSE; to determine transmissibility, brain material from index cases were inoculated into cattle.
In the first passage, cattle were intra-cranially challenged with brain homogenate from 2 Swiss animals with abnormal prionopathy. The challenged cattle incubated for 3 years and were euthanized with no clinical signs of neurologic disease. Animals were negative when tested on validated diagnostic tests but several research methods demonstrated changes in the prion conformation in these cattle, including density gradient centrifugation and immunohistochemistry. Currently, samples from the P1 animals are being tested for changes in protein levels using 2-D Fluorescence Difference Gel Electrophoresis (2D DIGE) and mass spectrometry. It is anticipated that, if a prionopathy is present, this approach should identify pathways and targets to decipher the source of altered protein conformation. In addition, a second set of cattle have been challenged with brain material from the first passage. Ideally, these cattle will be given a sufficient incubation period to provide a definitive answer to the question of transmissibility.
=====prion 2018===
Prion Conference 2018
Sunday, February 25, 2018
PRION ROUND TABLE CONFERENCE 2018 MAY, 22-25 A REVIW
Prion Conference 2018 Abstracts
https://hal.science/hal-04236401v1/file/Prion%202018%20book%20of%20abstracts%20180516.pdf
http://transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html
http://prionconference.blogspot.com/2018/
terry
