Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is a major health threat globally. Its prevalence is forecasted to exponentially increase during the next 30 years due to the global aging population. Currently, approved drugs are merely symptomatic, being ineffective in delaying or blocking the relentless disease advance. Intensive AD research describes this disease as a highly complex multifactorial disease. Disclosure of novel pathological pathways and their interconnections has had a major impact on medicinal chemistry drug development for AD over the last two decades. The complex network of pathological events involved in the onset of the disease has prompted the development of multitarget drugs. These chemical entities combine pharmacological activities toward two or more drug targets of interest. These multitarget‐directed ligands are proposed to modify different nodes in the pathological network aiming to delay or even stop disease progression. Here, we review the multitarget drug development strategy for AD during the last decade.

中文翻译：

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基于病理网络的创新多靶点治疗阿尔茨海默病

阿尔茨海默病（AD）是最常见的神经退行性疾病，是全球主要的健康威胁。由于全球人口老龄化，预计其患病率在未来 30 年将呈指数级增长。目前，批准的药物仅能缓解症状，无法有效延缓或阻止疾病的无情进展。深入的 AD 研究将这种疾病描述为一种高度复杂的多因素疾病。在过去的二十年里，新的病理途径及其相互联系的披露对 AD 的药物化学药物开发产生了重大影响。该疾病发病所涉及的病理事件的复杂网络促进了多靶点药物的开发。这些化学实体结合了针对两个或多个感兴趣的药物靶标的药理活性。这些多靶点定向配体被提议修改病理网络中的不同节点，旨在延缓甚至阻止疾病进展。在这里，我们回顾了过去十年中 AD 的多靶点药物开发策略。