Alzheimer's Disease, Oligomers, and Inflammation.
Alzheimer's Disease, Oligomers, and Inflammation.
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DOI：
10.3233/jad-170819
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Balducci C
中科院分区：
文献类型：
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作者：
Forloni G;Balducci C
可溶性β淀粉样蛋白寡聚体（AβOs）的产生和炎症的激活是阿尔茨海默病（AD）发病的两个重要早期阶段。寡聚体作为负责与临床特征相关的神经元功能障碍的中心作用已经扩展到其他蛋白质错误折叠疾病，在此基础上，定义为寡聚体病。在AD中，最近的证据表明，作为神经退行性变的结果的炎症机制必须进行评估，以支持神经胶质细胞活化在突触功能改变中的更直接作用。我们自己的实验模型证明了抗炎治疗在预防直接应用于大脑的Aβ O急性诱导的认知缺陷方面的功效。此外，一些有前途的临床工具是基于免疫激活减少脑Aβ沉积的存在。然而，基于控制炎症因子以及淀粉样蛋白聚集的策略显示出差的或非治疗功效。许多研究已经检查了生物流体中的炎症因子作为AD中神经炎症的可能标志物。在某些情况下，脑脊液中细胞因子或其他炎症标志物水平的改变与疾病的严重程度相关。在这里，我们提出，根据精准医学原则，创新的治疗方法，以AD患者的炎症概况/状态的基础上。早期干预和多因素方法是提高AD有效治疗机会的另外两个要素。
The production of soluble amyloid-β oligomers (AβOs) and the activation of inflammation are two important early steps in the pathogenesis of Alzheimer’s disease (AD). The central role of oligomers as responsible for the neuronal dysfunction associated with the clinical features has been extended to the other protein misfolding disorders definable, on this basis, as oligomeropathies. In AD, recent evidence indicates that the mechanism of inflammation as a consequence of neurodegeneration must be assessed in favor of a more direct role of glial activation in the alteration of synaptic function. Our own experimental models demonstrate the efficacy of anti-inflammatory treatments in preventing the cognitive deficits induced acutely by AβOs applied directly in the brain. Moreover, some promising clinical tools are based on immunological activation reducing the presence of cerebral Aβ deposits. However, the strategies based on the control of inflammatory factors as well as the amyloid aggregation show poor or non-therapeutic efficacy. Numerous studies have examined inflammatory factors in biological fluids as possible markers of the neuroinflammation in AD. In some cases, altered levels of cytokines or other inflammatory markers in cerebrospinal fluid correlate with the severity of the disease. Here we propose, according to the precision medicine principles, innovative therapeutic approaches to AD based on the patient’s inflammatory profile/state. The earlier intervention and a multifactor approach are two other elements considered essential to improve the chances of effective therapy in AD.