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HUMAN CIRCULATING MONOCYTES PHENOTYPES AND FUNCTIONS IN THE DEVELOPMENT OF ALZHEIMER’S DISEASE

Innovation in aging(2018)

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摘要
Alzheimer’ Disease is the most frequent neurocognitive disorder. The exact cause is not known however the neuroinflammation plays a key role. This neuroinflammation is more probably preceding the amyloid beta deposition in senile plaques. The innate immune system is playing a significant role in the neuroinflammation either in the brain (microglia) or in the periphery (monocytes). Our aim in the present work was to investigate the phenotypic and functional changes of monocytes in the progression of Alzheimer’s disease (AD). We evaluated four groups of subjects: healthy (HE), subjective memory complaint (SMC), amnestic Mild Cognitive Impairment (aMCI) and mildAD subjects (aged 60 to 85 years). We had 10 subjects per group. Monocytes were separated and studied by FACScan for their phenotypes and functions. Our results demonstrate that monocytes have a gradient of inflammatory phenotype (intermediate and non-classical) through the progression of the disease from HE to mAD subjects. The functions of monocytes are decreased through the progression of the disease. The differentiation of monocytes towards macrophages is skewed to the M1 phenotype. Our results demonstrate that monocytes may participate in the neuroinflammation as they cross the blood brain barrier and also as they become more and more inflammatory through the progression of the disease.
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