脑淀粉样血管病
体内
海马体
单核细胞
β淀粉样蛋白
病理
淀粉样蛋白(真菌学)
小胶质细胞
巨噬细胞
活体显微镜检查
管腔(解剖学)
早老素
炎症
神经科学
痴呆
阿尔茨海默病
生物
疾病
细胞生物学
医学
免疫学
体外
生物化学
生物技术
作者
Jean-Philippe Michaud,Marc‐André Bellavance,Paul Préfontaine,Serge Rivest
出处
期刊:Cell Reports
[Elsevier]
日期:2013-11-01
卷期号:5 (3): 646-653
被引量:209
标识
DOI:10.1016/j.celrep.2013.10.010
摘要
Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of Aβ deposition within the cerebral vasculature. The contribution of monocytes in AD has so far been limited to macrophage precursors. In this study, we aimed to investigate whether circulating monocytes could play a role in the elimination of Aβ. With live intravital two-photon microscopy, we demonstrate that patrolling monocytes are attracted to and crawl onto the luminal walls of Aβ-positive veins, but not on Aβ-positive arteries or Aβ-free blood vessels. Additionally, we report the presence of crawling monocytes carrying Aβ in veins and their ability to circulate back into the bloodstream. Selective removal of Ly6Clo monocytes in APP/PS1 mice induced a significant increase of Aβ load in the cortex and hippocampus. These data uncover the ability of Ly6Clo monocytes to naturally target and eliminate Aβ within the lumen of veins and constitute a potential therapeutic target in AD.
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