After years of failed therapeutic attempts targeting beta-amyloid (Aβ) in AD, there is now increasing evidence suggesting that inflammation holds a pivotal role in AD pathogenesis and immune pathways can possibly comprise primary therapeutic targets. Inflammation is a key characteristic of numerous diseases including neurodegenerative disorders and thus not surprisingly suppression of inflammation frequently constitutes a major therapeutic strategy for a wide spectrum of disorders. Several brain-resident and peripherally-derived immune populations and inflammatory mediators are involved in AD pathophysiology, with microglia comprising central cellular player in the disease process. Systemic inflammation, mostly in the form of infections, has long been observed to induce behavioral alterations and cognitive dysfunction, suggesting for a close interaction of the peripheral immune system with the brain. Systemic inflammation can result in neuroinflammation, mainly exhibited as microglial activation, production of inflammatory molecules, as well as recruitment of peripheral immune cells in the brain, thus shaping a cerebral inflammatory milieu that may seriously impact neuronal function. Increasing clinical and experimental studies have provided significant evidence that acute (e.g. infections) or chronic (e.g. autoimmune diseases like rheumatoid arthritis) systemic inflammatory conditions may be associated with increased AD risk and accelerate AD progression. Here we review the current literature that links systemic with CNS inflammation and the implications of this interaction for AD in the context of acute and chronic systemic pathologies as acute infection and rheumatoid arthritis. Elucidating the mechanisms that govern the crosstalk between the peripheral and the local brain immune system may provide the ground for new therapeutic approaches that target the immune-brain interface and shed light on the understanding of AD.

中文翻译：

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系统性和中枢神经系统炎症串扰：对阿尔茨海默氏病的影响。

在针对AD中的β-淀粉样蛋白（Aβ）的治疗尝试失败了数年之后，现在越来越多的证据表明炎症在AD发病机理中起着关键作用，免疫途径可能包含主要的治疗靶点。炎症是包括神经退行性疾病在内的许多疾病的关键特征，因此不足为奇的是，炎症抑制常构成广泛疾病的主要治疗策略。AD病理生理学涉及几种大脑驻留和外周来源的免疫种群和炎性介质，小胶质细胞在疾病过程中构成中心细胞。长期以来，人们普遍观察到全身性炎症（主要是感染形式）会诱发行为改变和认知功能障碍，提示外围免疫系统与大脑的紧密相互作用。全身性炎症可导致神经炎症，主要表现为小胶质细胞活化，炎症分子的产生以及大脑中周围免疫细胞的募集，从而形成可能严重影响神经元功能的大脑炎症环境。越来越多的临床和实验研究提供了重要的证据，表明急性（例如感染）或慢性（例如类风湿性关节炎等自身免疫性疾病）系统性炎症可能与AD风险增加和AD进展有关。在这里，我们回顾了将全身性与中枢神经系统炎症联系起来的文献，以及这种相互作用对急性和慢性全身性疾病（如急性感染和类风湿关节炎）的影响。阐明控制外周和局部大脑免疫系统之间的串扰的机制，可以为针对免疫脑接口并阐明对AD的理解的新治疗方法提供基础。