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Implication des polynucléaires neutrophiles au cours de la maladie d’Alzheimer et des tauopathies

Abstract : Neutrophils are key components of early innate immunity and contribute to uncontrolled systemic inflammation if not tightly regulated. Our study demonstrated that blood samples from Alzheimer’s Disease (AD) patients with dementia revealed neutrophil hyperactivation associated with increased reactive oxygen species (ROS) 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 latter stage of the disease. These abnormalities, that may play an instrumental role in establishing systemic chronic inflammation, were greater in fast-decliner than in slow-decliner patients. Some abnormalities, including the increased level of ROS production, were observed in patients with atypic AD but not in Tauopathies suggesting that these alterations are specific of amyloid pathology. Our data strongly suggest that the neutrophil phenotype may constitute an innovative and prognostic blood biomarker in patients with Alzheimer’s disease open new perspectives for the development of innovative immunotherapy strategies based on neutrophil modulation.
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Yuan Dong. Implication des polynucléaires neutrophiles au cours de la maladie d’Alzheimer et des tauopathies. Immunologie. Sorbonne Université, 2018. Français. ⟨NNT : 2018SORUS445⟩. ⟨tel-02937879⟩

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