Alzheimer disease (AD) accounts for 60–70% of dementia cases. Given the seriousness of the disease and continual increase in patient numbers, developing effective therapies to treat AD has become urgent. Presently, the drugs available for AD treatment, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate receptor, can only inhibit dementia symptoms for a limited period of time but cannot stop or reverse disease progression. On the basis of the amyloid hypothesis, many global drug companies have conducted many clinical trials on amyloid clearing therapy but without success. Thus, the amyloid hypothesis may not be completely feasible. The number of anti-amyloid trials decreased in 2019, which might be a turning point. An in-depth and comprehensive understanding of the contribution of amyloid beta and other factors of AD is crucial for developing novel pharmacotherapies. In ongoing clinical trials, researchers have developed and are testing several possible interventions aimed at various targets, including anti-amyloid and anti-tau interventions, neurotransmitter modification, anti-neuroinflammation and neuroprotection interventions, and cognitive enhancement, and interventions to relieve behavioral psychological symptoms. In this article, we present the current state of clinical trials for AD at clinicaltrials.gov. We reviewed the underlying mechanisms of these trials, tried to understand the reason why prior clinical trials failed, and analyzed the future trend of AD clinical trials.

中文翻译：

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阿尔茨海默病新药临床试验

阿尔茨海默病 (AD) 占痴呆病例的 60-70%。鉴于疾病的严重性和患者数量的不断增加，开发有效的治疗方法来治疗 AD 已刻不容缓。目前治疗AD的药物，包括胆碱酯酶抑制剂和N-甲基-D-天冬氨酸受体拮抗剂，只能在有限的时间内抑制痴呆症状，而不能阻止或逆转疾病进展。基于淀粉样蛋白假说，全球多家制药公司针对淀粉样蛋白清除疗法进行了多项临床试验，但均未取得成功。因此，淀粉样蛋白假说可能并不完全可行。2019 年抗淀粉样蛋白试验的数量有所减少，这可能是一个转折点。深入全面地了解β淀粉样蛋白和AD其他因素的贡献对于开发新型药物疗法至关重要。在正在进行的临床试验中，研究人员已经开发并正在测试针对不同目标的几种可能的干预措施，包括抗淀粉样蛋白和抗 tau 干预措施、神经递质修饰、抗神经炎症和神经保护干预措施、认知增强以及缓解行为心理症状的干预措施。在本文中，我们介绍了 ClinicalTrials.gov 上 AD 临床试验的现状。我们回顾了这些试验的潜在机制，试图了解先前临床试验失败的原因，并分析AD临床试验的未来趋势。