Alzheimer's disease is characterized by cognitive alterations, cerebral atrophy and neuropathological lesions including neuronal loss, accumulation of misfolded and aggregated β-amyloid peptides (Aβ) and tau proteins. Iatrogenic induction of Aβ is suspected in patients exposed to pituitary-derived hormones, dural grafts, or surgical instruments, presumably contaminated with Aβ. Induction of Aβ and tau lesions has been demonstrated in transgenic mice after contamination with Alzheimer's disease brain homogenates, with very limited functional consequences. Unlike rodents, primates naturally express Aβ or tau under normal conditions and attempts to transmit Alzheimer pathology to primates have been made for decades. However, none of earlier studies performed any detailed functional assessments. For the first time we demonstrate long term memory and learning impairments in a non-human primate (Microcebus murinus) following intracerebral injections with Alzheimer human brain extracts. Animals inoculated with Alzheimer brain homogenates displayed progressive cognitive impairments (clinical tests assessing cognitive and motor functions), modifications of neuronal activity (detected by electroencephalography), widespread and progressive cerebral atrophy (in vivo MRI assessing cerebral volume loss using automated voxel-based analysis), neuronal loss in the hippocampus and entorhinal cortex (post mortem stereology). They displayed parenchymal and vascular Aβ depositions and tau lesions for some of them, in regions close to the inoculation sites. Although these lesions were sparse, they were never detected in control animals. Tau-positive animals had the lowest performances in a memory task and displayed the greatest neuronal loss. Our study is timely and important as it is the first one to highlight neuronal and clinical dysfunction following inoculation of Alzheimer's disease brain homogenates in a primate. Clinical signs in a chronic disease such as Alzheimer take a long time to be detectable. Documentation of clinical deterioration and/or dysfunction following intracerebral inoculations with Alzheimer human brain extracts could lead to important new insights about Alzheimer initiation processes.

中文翻译：

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在非人类灵长类动物中由阿尔茨海默氏病脑部接种诱发的脑病。

阿尔茨海默氏病的特征是认知改变，脑萎缩和神经病理损害，包括神经元丢失，错折叠和聚集的β-淀粉样肽（Aβ）和tau蛋白积聚。怀疑患有垂体源性激素，硬脑膜移植物或手术器械（可能被Aβ污染）的患者会引起Aβ的医源性诱导。在被阿尔茨海默氏病脑匀浆污染后，在转基因小鼠中已经证明了Aβ和tau损伤的诱导，其功能后果非常有限。与啮齿动物不同，灵长类动物在正常条件下自然表达Aβ或tau，并且已经尝试将阿尔茨海默氏病传播给灵长类动物。但是，早期的研究都没有进行任何详细的功能评估。我们首次在脑内注射阿尔茨海默氏症人脑提取物后证明了非人灵长类动物（Microcebus murinus）的长期记忆和学习障碍。接种阿尔茨海默氏脑匀浆的动物表现出进行性认知障碍（评估认知和运动功能的临床测试），神经元活动的改变（通过脑电图检测），广泛和进行性脑萎缩（体内MRI使用基于自动体素的分析评估脑体积损失） ，海马和内嗅皮层的神经元丢失（验尸）。它们在靠近接种部位的区域中显示出其中一些的实质和血管Aβ沉积和tau病变。尽管这些病变很少，但在对照动物中从未发现。Tau阳性动物在记忆任务中表现最低，并表现出最大的神经元丢失。我们的研究是及时而重要的，因为这是在灵长类动物接种阿尔茨海默氏病脑匀浆后首次强调神经元和临床功能障碍的研究。诸如阿尔茨海默氏症这样的慢性疾病的临床体征需要很长时间才能被发现。脑内接种阿尔茨海默氏症人脑提取物后临床恶化和/或功能障碍的文献记录可能会导致有关阿尔茨海默氏症起始过程的重要新见解。氏病的大脑在灵长类动物中匀浆。诸如阿尔茨海默氏症这样的慢性疾病的临床体征需要很长时间才能被发现。脑内接种阿尔茨海默氏症人脑提取物后临床恶化和/或功能障碍的文献记录可能会导致有关阿尔茨海默氏症起始过程的重要新见解。氏病的大脑在灵长类动物中匀浆。诸如阿尔茨海默氏症这样的慢性疾病的临床体征需要很长时间才能被发现。脑内接种阿尔茨海默氏症人脑提取物后临床恶化和/或功能障碍的文献记录可能会导致有关阿尔茨海默氏症起始过程的重要新见解。