Neutrophil hyperactivation correlates with Alzheimer's disease progression

被引：123

作者：

Dong, Yuan ^{[1
]}

Lagarde, Julien ^{[2
,3
]}

Xicota, Laura ^{[4
]}

Corne, Helene ^{[2
]}

Chantran, Yannick ^{[1
]}

Chaigneau, Thomas ^{[1
]}

Crestani, Bruno ^{[5
]}

Bottlaender, Michel ^{[3
,6
]}

Potier, Marie-Claude ^{[4
]}

Aucouturier, Pierre ^{[1
]}

Dorothee, Guillaume ^{[1
]}

Sarazin, Marie ^{[2
,3
]}

Elbim, Carole ^{[1
]}

机构：

[1] UPMC Univ Paris 06, Sorbonne Univ, Team Immune Syst Neuroinflammat & Neurodegenerat, INSERM,Ctr Rech St Antoine,Hop St Antoine, Paris, France

[2] Univ Paris 05, Unit Neurol Memory & Language, Ctr Hosp St Anne, Sorbonne Paris Cite, Paris, France

[3] Univ Paris Sud, CEA, INSERM,I2BM,Serv Hosp Frederic Joliot, Lab Imagerie Mol Vivo IMIV,ERL 9218,CNRS,UMR 1023, Orsay, France

[4] UPMC Univ Paris 06, Sorbonne Univ, CNRS,ICM, UMR 7225,INSERM,U1127,UMRS 1127,Inst Cerveau & Mo, Paris, France

[5] Hop Bichat Claude Bernard, AP HP, Serv Pneumol A, Ctr Reference Malad Pulm Rares, Paris, France

[6] Commissariat Energie Atom, UNIACT, NeuroSpin, Direct Sci Vivant,Inst Imagerie Biomed, Gif Sur Yvette, France

来源：

ANNALS OF NEUROLOGY | 2018年 / 83卷 / 02期

关键词：

BRAIN-BARRIER IMPAIRMENT; POLYMORPHONUCLEAR NEUTROPHILS; MICROGLIAL ACTIVATION; EXTRACELLULAR TRAPS; WHOLE-BLOOD; PROINFLAMMATORY CYTOKINES; SYSTEMIC INFLAMMATION; OXIDATIVE BURST; GENE-EXPRESSION; CELL-DEATH;

D O I：

10.1002/ana.25159

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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

引用

页码：387 / 405

页数：19

共 86 条

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