Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY, 10016, USA; Department of Neuroscience Institute, New York University School of Medicine, New York, NY, 10016, USA.
Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY, 10016, USA; Department of Psychiatry, New York University School of Medicine, New York, NY, 10016, USA; Department of Neuroscience Institute, New York University School of Medicine, New York, NY, 10016, USA.
Neuropharmacology. 2020 Sep 15;175:108104. doi: 10.1016/j.neuropharm.2020.108104. Epub 2020 Apr 28.
The majority of clinical trials targeting the tau protein in Alzheimer's disease and other tauopathies are tau immunotherapies. Because tau pathology correlates better with the degree of dementia than amyloid-β lesions, targeting tau is likely to be more effective in improving cognition than clearing amyloid-β in Alzheimer's disease. However, the development of tau therapies is in many ways more complex than for amyloid-β therapies as briefly outlined in this review. Most of the trials are on humanized antibodies, which may have very different properties than the original mouse antibodies. The impact of these differences are to a large extent unknown, can be difficult to decipher, and may not always be properly considered. Furthermore, the ideal antibody properties for efficacy are not well established and can depend on several factors. However, considering the varied approaches in clinical trials, there is a general optimism that at least some of these trials may provide functional benefits to patients suffering of various tauopathies. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
大多数针对阿尔茨海默病和其他tau 病tau 蛋白的临床试验都是 tau 免疫疗法。由于 tau 病理学与痴呆程度的相关性优于淀粉样蛋白-β 病变，因此针对 tau 的治疗可能比清除阿尔茨海默病中的淀粉样蛋白-β更有效地改善认知。然而，tau 疗法的开发在许多方面比淀粉样蛋白-β 疗法更为复杂，如本综述简要概述的那样。大多数试验都是针对人源化抗体的，这些抗体可能与原始的小鼠抗体具有非常不同的特性。这些差异的影响在很大程度上是未知的，难以解读，并且可能并不总是得到适当的考虑。此外，疗效理想的抗体特性尚未得到很好的确定，并且可能取决于几个因素。然而，考虑到临床试验中的各种方法，人们普遍乐观地认为，这些试验中的至少一些可能会为患有各种 tau 病的患者提供功能益处。本文是特刊“神经退行性疾病的疾病修饰治疗探索”的一部分。
