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Πέμπτη 25 Ιανουαρίου 2018

Neutrophil hyperactivation correlates with Alzheimer's disease progression

Abstract

Objective: Recent studies have underlined the effect of systemic inflammation on the pathophysiology of Alzheimer's disease. 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 Alzheimer's disease.

Methods: We analyzed neutrophil phenotypes and functions in forty-two patients with Alzheimer's disease (sixteen with mild cognitive impairment and twenty-six with dementia), and compared them with twenty-two 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 Alzheimer's diseases 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 CXCR4high/CD62Llow senescent and the CD16bright/CD62Ldim 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 Alzheimer's disease — 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 Alzheimer's disease. This article is protected by copyright. All rights reserved.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2napZap

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