Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer’s disease

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• 作者：Ben J. Gu ; Xin Huang ; Amber Ou ; Alan Rembach ; Christopher Fowler…
• 刊名：Acta Neuropathologica
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：132
• 期：3
• 页码：377-389
• 全文大小：2,214 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Pathology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0533
• 卷排序：132

文摘

Sporadic Alzheimer’s disease (AD) is characterised by the deposition and accumulation of specific protein aggregates. Failure of clearance could underlie this process, and recent genetic association studies point towards involvement of the phagocytosis and autophagy pathways. We developed a real-time tri-color flow cytometry method to quantitate the phagocytic function of human peripheral blood monocyte subsets including non-classic CD14dimCD16+, intermediate CD14+CD16+ and classic CD14+CD16− monocytes. Using this method, we have measured the phagocytic ability of fresh monocytes in a study of preclinical, prodromal and clinical AD, matched with cognitively normal healthy control subjects. Basal levels of phagocytosis in all three subsets of monocytes were similar between healthy controls and AD patients, while a significant increase of basal phagocytosis was found in subjects with high Aβ-amyloid burden as assessed by PET scans. Pre-treating cells with Copaxone (CPX, to stimulate phagocytosis) or ATP (an inhibitor of P2X7-mediated phagocytosis) showed a differential response depending on clinical or Aβ-burden status, indicating a relative functional deficit. Overall the results are consistent with a perturbation of basal and stimulated innate phagocytosis in sporadic AD.KeywordsPhagocytosisAlzheimer’s diseaseCopaxone (glatiramer acetate)ATPP2X7