Galimberti Daniela, Fenoglio Chiara, Scarpini Elio
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Ospedale Maggiore Policlinico IRCCS, Via F. Sforza 35, 20122, Milan, Italy.
Curr Aging Sci. 2008 Mar;1(1):30-41. doi: 10.2174/1874609810801010030.
Inflammation plays a role in the development of Alzheimer's disease (AD). Several cytokines and chemokines have been detected both immunohistochemically and in cerebrospinal fluid from patients. Some of them, including Tumor Necrosis Factor-alpha, Interferon-gamma-inducible Protein-10, Monocyte Chemotactic Protein-1 and Interleukin-8, are increased in AD and in Mild Cognitive Impairment (MCI), considered the prodromal stage of AD, suggesting that these modifications occur very early during the development of the disease, possibly explaining the failure of trials with anti-inflammatory agents in patients with severe AD. Further evidence suggests that cytokines and chemokines could have a role in other neurodegenerative disorders, such as Frontotemporal Lobar Degeneration and Amyothrophic Lateral Sclerosis. In this regard, analogies and differences among these neurodegenerative disorders will be discussed. Neurodegenerative disorders are considered multifactorial diseases, and genetic factors influence pathological events and contribute to change the disease phenotype from patient to patient. Gene polymorphisms in crucial molecules, including cytokines, chemokines and molecules related to oxidative stress, may act as susceptibility factors, increasing the risk of disease development, or may operate as regulatory factors, modulating the severity of pathogenic processes or the response to drug treatment. With these premises, genetic studies recently carried out will be described and discussed in detail.
炎症在阿尔茨海默病（AD）的发展过程中起作用。通过免疫组织化学方法以及在患者的脑脊液中均检测到了多种细胞因子和趋化因子。其中一些因子，包括肿瘤坏死因子-α、干扰素-γ诱导蛋白-10、单核细胞趋化蛋白-1和白细胞介素-8，在AD以及被认为是AD前驱期的轻度认知障碍（MCI）中均有所增加，这表明这些变化在疾病发展的早期阶段就已发生，这可能解释了针对重度AD患者的抗炎药物试验为何失败。进一步的证据表明，细胞因子和趋化因子可能在其他神经退行性疾病中起作用，如额颞叶痴呆和肌萎缩侧索硬化症。在这方面，将讨论这些神经退行性疾病之间的异同。神经退行性疾病被认为是多因素疾病，遗传因素影响病理事件，并导致不同患者的疾病表型发生变化。关键分子的基因多态性，包括细胞因子、趋化因子以及与氧化应激相关的分子，可能作为易感性因素增加疾病发生的风险，或者作为调节因子调节致病过程的严重程度或对药物治疗的反应。基于这些前提，将详细描述和讨论最近进行的基因研究。
