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Immunotherapy for Alzheimer’s disease: hoops and hurdles

机译：阿尔茨海默氏病的免疫疗法：箍和障碍

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摘要

Alzheimer’s disease (AD) is the most common form of dementia, afflicting more than 30 million people worldwide. Currently, there is no cure or way to prevent this devastating disease. Extracellular plaques, containing various forms of amyloid-β protein (Aβ), and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated tau protein, are two major pathological hallmarks of the AD brain. Aggregation, deposition, and N-terminal modification of Aβ protein and tau phosphorylation and aggregation are thought to precede the onset of cognitive decline, which is better correlated with tangle formation and neuron loss. Active and passive vaccines against various forms of Aβ have shown promise in pre-clinical animal models. However, translating these results safely and effectively into humans has been challenging. Recent clinical trials showed little or no cognitive efficacy, possibly due to the fact that the aforementioned neurodegenerative processes most likely pre-existed in the patients well before the start of immunotherapy. Efforts are now underway to treat individuals at risk for AD prior to or in the earliest stages of cognitive decline with the hope of preventing or delaying the onset of the disease. In addition, efforts to immunize against tau and other AD-related targets are underway.
机译：阿尔茨海默氏病（AD）是痴呆症最常见的形式，全世界有3000万人受其折磨。当前，没有治愈或预防这种破坏性疾病的方法。含有各种形式的淀粉样β蛋白（Aβ）的细胞外斑块和由磷酸化tau蛋白组成的细胞内神经原纤维缠结（NFT）是AD脑的两个主要病理标志。 Aβ蛋白的聚集，沉积和N末端修饰以及tau磷酸化和聚集被认为是在认知功能减退之前发生的，这与缠结的形成和神经元的丧失更好相关。在临床前动物模型中，针对各种形式的Aβ的主动和被动疫苗已显示出希望。然而，将这些结果安全有效地转化为人类一直是一项挑战。最近的临床试验显示出很少或没有认知功效，这可能是由于上述神经变性过程最有可能在免疫治疗开始之前就已经存在于患者中这一事实。现在正在努力治疗在认知能力减退之前或最早阶段有AD风险的个体，以期预防或延缓疾病的发作。另外，正在进行针对tau和其他AD相关靶标的免疫接种的努力。

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