Alzheimer's Disease (AD) is the most common neurodegenerative disease and cause of dementia. Characterized by amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau, AD pathology has been intensively studied during the last century. After a long series of failed trials of drugs targeting amyloid or Tau deposits, currently, hope lies in the positive results of one Phase III trial, highly debated, and on other ongoing trials. In parallel, some approaches target neuroinflammation, another central feature of AD. Therapeutic strategies are initially evaluated on animal models, in which the various drugs have shown effects on the target (decreasing amyloid, Tau and neuroinflammation) and sometimes on cognitive impairment. However, it is important to keep in mind that rodent models have a less complex brain than humans and that the pathology is generally not fully represented. Although they are indispensable tools in the drug discovery process, results obtained from animal models must be viewed with caution. In this review, we focus on the current status of disease-modifying therapies targeting amyloid, Tau and neuroinflammation with particular attention on the discrepancy between positive preclinical results on animal models and failures in clinical trials.

中文翻译：

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从过去的经验中学习：针对阿尔茨海默氏病中的淀粉样蛋白，Tau和神经炎症的临床试验综述。

阿尔茨海默氏病（AD）是最常见的神经退行性疾病和痴呆症的病因。AD病理学以淀粉样蛋白斑块和高磷酸化Tau的神经原纤维缠结为特征，在上个世纪已被深入研究。在针对淀粉样蛋白或Tau沉积物的药物进行了一系列长期失败的试验之后，目前，人们寄希望于一项备受争议的III期临床试验的积极结果以及其他正在进行的试验。同时，一些方法针对神经炎症，这是AD的另一个主要特征。最初在动物模型上评估了治疗策略，其中各种药物均显示出对靶标的作用（减少淀粉样蛋白，Tau和神经炎症），有时还对认知障碍产生影响。然而，重要的是要记住，啮齿动物模型的大脑比人类的大脑复杂，并且病理通常不能完全体现。尽管它们是药物发现过程中必不可少的工具，但必须谨慎对待从动物模型获得的结果。在这篇综述中，我们重点关注针对淀粉样蛋白，Tau和神经炎症的疾病改良疗法的当前状态，特别关注动物模型的临床前阳性结果与临床试验失败之间的差异。