Galimberti Daniela, Scarpini Elio
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy.
Front Biosci (Schol Ed). 2011 Jan 1;3(1):252-66. doi: 10.2741/s149.
The two major neuropathologic hallmarks of AD are extracellular Amyloid beta plaques and intracellular neurofibrillary tangles. A number of additional pathogenic mechanisms have been described, including inflammation and oxidative damage. Regarding inflammation, 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, 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 play a role in other neurodegenerative disorders. These 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, or may operate as regulatory factors, modulating the severity of pathogenic processes.
阿尔茨海默病（AD）的两大主要神经病理学特征是细胞外β淀粉样蛋白斑块和细胞内神经原纤维缠结。人们还描述了许多其他致病机制，包括炎症和氧化损伤。关于炎症，在患者的免疫组织化学检测和脑脊液中均检测到了多种细胞因子和趋化因子。其中一些，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中均有所增加，这表明这些变化在疾病发展过程中很早就出现了，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。这些疾病被认为是多因素疾病，遗传因素会影响病理事件，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、趋化因子和与氧化应激相关的分子，可能作为易感因素，或作为调节因子，调节致病过程的严重程度。
