Neutrophil hyperactivation correlates with Alzheimer's disease progression
Neutrophil hyperactivation correlates with Alzheimer's disease progression
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DOI：
10.1002/ana.25159
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发表时间：
2018-02-01
影响因子：
11.2
通讯作者：
Elbim, Carole
中科院分区：
文献类型：
--
作者：
Dong, Yuan;Lagarde, Julien;Elbim, Carole
最近的研究强调了全身炎症对阿尔茨海默病（AD）病理生理学的影响。中性粒细胞是早期先天免疫的关键组成部分，如果不严格调节，则会导致不受控制的全身炎症。我们的研究的目的是充分表征人类循环中性粒细胞在不同的疾病阶段AD。MethodsWe分析了42例AD患者（16例轻度认知功能障碍和26例痴呆）的中性粒细胞表型和功能，并将其与22名年龄匹配的健康受试者进行比较。这项研究直接在全血中进行，以避免与细胞分离procedures. ResultsAD痴呆患者的血液样本中的数据解释的问题，发现中性粒细胞过度活化与活性氧产生增加和血管内中性粒细胞血管外陷阱的水平增加。这些患者的循环中性粒细胞的稳态也发生了变化：在疾病的后期，有害的高反应性CXCR 4（高）/CD 62 L（低）衰老和CD 16（亮）/CD 62 L（暗）免疫抑制中性粒细胞亚群之间的比例上升。这些异常是更大的快速下降比在缓慢下降patients.InterpretationOur的结果表明，循环中性粒细胞的炎症性质的变化，老年中性粒细胞的百分比扩大在AD患者的变化，可能发挥了重要作用，在建立系统性慢性炎症。最重要的是，我们的数据强烈表明，中性粒细胞表型可能与认知能力下降的速度，因此可能构成一个创新的和预后的血液生物标志物在AD患者。神经学年鉴2018;83：387-405
ObjectiveRecent studies have underlined the effect of systemic inflammation on the pathophysiology of Alzheimer's disease (AD). Neutrophils are key components of early innate immunity and contribute to uncontrolled systemic inflammation if not tightly regulated. The aim of our study was to fully characterize human circulating neutrophils at different disease stages in AD.MethodsWe analyzed neutrophil phenotypes and functions in 42 patients with AD (16 with mild cognitive impairment and 26 with dementia), and compared them to 22 age-matched healthy subjects. This study was performed directly in whole blood to avoid issues with data interpretation related to cell isolation procedures.ResultsBlood samples from AD patients with dementia revealed neutrophil hyperactivation associated with increased reactive oxygen species production and increased levels of intravascular neutrophil extravascular traps. The homeostasis of circulating neutrophils in these patients also changed: The ratio between the harmful hyperreactive CXCR4(high)/CD62L(low) senescent and the CD16(bright)/CD62L(dim) immunosuppressive neutrophil subsets rose in the later stage of the disease. These abnormalities were greater in fast-decliner than in slow-decliner patients.InterpretationOur results indicate that the inflammatory properties of circulating neutrophils shift as the percentage of aged neutrophils expands in patients with ADchanges that may play an instrumental role in establishing systemic chronic inflammation. Most important, our data strongly suggest that the neutrophil phenotype may be associated with the rate of cognitive decline and may thus constitute an innovative and prognostic blood biomarker in patients with AD. Ann Neurol 2018;83:387-405