Immunotherapy for Alzheimer's disease: hoops and hurdles.
Immunotherapy for Alzheimer's disease: hoops and hurdles.
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DOI：
10.1186/1750-1326-8-36
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发表时间：
2013-10-22
影响因子：
15.1
通讯作者：
Lemere CA
中科院分区：
文献类型：
--
作者：
Lemere CA
阿尔茨海默病 (AD) 是最常见的痴呆症，全世界有超过 3000 万人受其困扰。目前，还没有治愈方法或方法来预防这种毁灭性的疾病。含有各种形式的淀粉样β蛋白（Aβ）的细胞外斑块和由过度磷酸化的tau蛋白组成的细胞内神经原纤维缠结（NFT）是AD大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先于认知能力下降，而认知能力下降与缠结形成和神经元损失更好相关。针对各种形式 Aβ 的主动和被动疫苗已在临床前动物模型中显示出前景。然而，将这些结果安全有效地转化为人类一直具有挑战性。最近的临床试验显示很少或没有认知功效，可能是由于上述神经退行性过程很可能在免疫治疗开始之前就已经存在于患者体内。目前正在努力治疗认知能力下降之前或早期阶段有 AD 风险的个体，希望能够预防或延缓该疾病的发作。此外，针对 tau 蛋白和其他 AD 相关目标的免疫工作正在进行中。
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.
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影响因子：
4
作者：
Bohrmann, Bernd;Baumann, Karlheinz;Loetscher, Hansruedi
通讯作者：
Loetscher, Hansruedi
影响因子：
14
作者：
Farlow, Martin;Amold, Steven E.;Siemers, Eric R.
通讯作者：
Siemers, Eric R.
影响因子：
14
作者：
Thies, William;Bleiler, Laura
通讯作者：
Bleiler, Laura
DOI：
10.1073/pnas.151261398
发表时间：
2001-07-17
影响因子：
11.1
作者：
DeMattos, RB;Bales, KR;Holtzman, DM
通讯作者：
Holtzman, DM
影响因子：
82.9
作者：
Lemere, CA;Lopera, F;Arango, JCV
通讯作者：
Arango, JCV