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
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
科研通智能强力驱动
Strongly Powered by AbleSci AI