Moreno-Gonzalez Ines, Edwards George, Morales Rodrigo, Duran-Aniotz Claudia, Escobedo Gabriel, Marquez Mercedes, Pumarola Marti, Soto Claudio
Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Health Science Center at Houston, Houston, TX, United States.
Departamento Biología Celular, Genética y Fisiología, Instituto de Investigacion Biomedica de Malaga-IBIMA, Universidad de Malaga, Malaga, Spain.
Front Aging Neurosci. 2022 Jan 31;13:815361. doi: 10.3389/fnagi.2021.815361. eCollection 2021.
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.
阿尔茨海默病（AD）是晚年痴呆的主要病因之一。尽管AD神经退行性变的病因尚未完全明确，但大量证据表明，淀粉样β蛋白（Aβ）和tau蛋白的错误折叠、聚集以及在大脑中的蓄积是标志性事件。最近的报告显示，少量预先形成的聚集体的给药可诱导蛋白质错误折叠和聚集，这与朊病毒疾病可通过感染传播的原理类似。在过去几年中，Aβ聚集体也表现出了许多将朊病毒表征为传染因子的典型特性。有趣的是，朊病毒疾病不仅影响人类，还影响各种哺乳动物，并且已经证明动物组织中存在的传染性朊病毒，特别是受牛海绵状脑病（BSE）影响的牛，可感染人类。据报道，在包括猴子、熊、狗和猎豹在内的几种老年非人类哺乳动物的大脑中存在类似Aβ淀粉样斑块的蛋白质沉积物。在本研究中，我们调查了老年牛大脑中Aβ聚集体的存在情况、它们与AD患者中观察到的蛋白质沉积物的相似性，以及将其脑内接种到AD转基因动物模型中促进AD病理特征的能力。我们的数据表明，从组织学研究来看，老年牛可出现类似AD的神经病理异常，包括淀粉样斑块。重要的是，牛源性聚集体加速了AD转基因动物大脑中Aβ淀粉样沉积。令人惊讶的是，给予牛源材料产生的诱导率明显高于注射等量人类AD材料产生的诱导率。我们的研究结果表明，牛会形成具有播种能力的Aβ聚集体，这与在AD患者中观察到的情况类似。
