Aged Cattle Brain Displays Alzheimer's Disease-Like Pathology and Promotes Brain Amyloidosis in a Transgenic Animal Model
Moreno-Gonzalez, Ines (Universidad Bernardo O'Higgins. Centro Integrativo de Biologia y Quimica Aplicada)
Edwards, George (University of Texas. Mitchell Center for Alzheimer's Disease and Related Brain Disorders)
Morales, Rodrigo (Universidad Bernardo O'Higgins. Centro Integrativo de Biologia y Quimica Aplicada)
Duran-Aniotz, Claudia (Universidad Adolfo Ibañez. Latin American Institute for Brain Health)
Escobedo, Gabriel (University of Texas. Mitchell Center for Alzheimer's Disease and Related Brain Disorders)
Pumarola i Batlle, Martí (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Marquez, Mercedes (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Soto, Claudio (University of Texas. Mitchell Center for Alzheimer's Disease and Related Brain Disorders)

Fecha:	2022
Resumen:	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.
Ayudas:	Ministerio de Ciencia, Innovación y Universidades PID2019-107090RA-I00 Ministerio de Ciencia, Innovación y Universidades RYC-2017-21879
Nota:	Altres ajuts: Alzheimer's Association AARGD-18-566576 i NIRP-12-257323. National Institutes of Health RF1AG072491
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Amyloid ; Prions ; Alzheimer's disease ; Spreading ; Protein misfolding ; Seeding ; Cattle
Publicado en:	Frontiers in aging neuroscience, Vol. 13 (january 2022) , ISSN 1663-4365

DOI: 10.3389/fnagi.2021.815361
PMID: 35173603

10 p, 1.4 MB

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