Neutrophil hyperactivation correlates with Alzheimer's disease progression

炎症 全身炎症 痴呆 CD16 免疫学 医学 认知功能衰退 病理生理学 生物标志物 全血 先天免疫系统 疾病 内科学 阿尔茨海默病 生物 免疫系统 CD8型 CD3型 生物化学
作者
Yuan Dong,Julien Lagarde,Laura Xicota,Hélène Corne,Yannick Chantran,Thomas Chaigneau,Bruno Crestani,Michel Bottlaender,Marie‐Claude Potier,Pièrre Aucouturier,Guillaume Dorothée,Marie Sarazin,Carole Elbim
出处
期刊:Annals of Neurology [Wiley]
卷期号:83 (2): 387-405 被引量:116
标识
DOI:10.1002/ana.25159
摘要

Objective Recent 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. Methods We 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. Results Blood 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. Interpretation Our results indicate that the inflammatory properties of circulating neutrophils shift as the percentage of aged neutrophils expands in patients with AD—changes 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
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