Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, P.O. Box 1627, Kuopio, Finland.
Glia. 2010 Jun;58(8):889-900. doi: 10.1002/glia.20973.
Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a cure. The abnormal parenchymal accumulation of beta-amyloid (Abeta) is associated with inflammatory reactions involving microglia and astrocytes. Increased levels of Abeta and Abeta deposition in the brain are thought to cause neuronal dysfunction and underlie dementia. Microglia, the brain resident cells of monocytic origin, have a potential ability to phagocytose Abeta but they also react to Abeta by increased production of proinflammatory toxic agents. Microglia originate from hemangioblastic mesoderm during early embryonic stages and from bone marrow (BM)-derived monocytic cells that home the brain throughout the neonatal stage of development. Recent studies indicate that BM or blood-derived monocytes are recruited to the diseased AD brain, associate with the Abeta depositions, and are more efficient phagocytes of Abeta compared with resident microglia. The clearance of Abeta deposition by these cells has been recently under intensive investigation and can occur through several different mechanisms. Importantly, peripheral monocytic cells of patients with AD appear to be deficient in clearing Abeta. This review will summarize the findings on the role of blood-derived cells in AD and discuss their therapeutic potential for treating patients suffering from this devastating disease.
阿尔茨海默病（AD）是一种无法治愈的神经退行性痴呆症。β-淀粉样蛋白（Abeta）的异常实质积累与涉及小胶质细胞和星形胶质细胞的炎症反应有关。脑内 Abeta 水平升高和 Abeta 沉积被认为导致神经元功能障碍，并构成痴呆的基础。小胶质细胞是单核细胞来源的脑固有细胞，具有吞噬 Abeta 的潜在能力，但它们也通过增加产生促炎毒性物质来对 Abeta 产生反应。小胶质细胞在早期胚胎阶段起源于血管母细胞中胚层，来自骨髓（BM）衍生的单核细胞，在发育的新生儿阶段归巢到大脑。最近的研究表明，BM 或血液来源的单核细胞被募集到患病的 AD 大脑中，与 Abeta 沉积相关，并且比固有小胶质细胞更有效地吞噬 Abeta。这些细胞清除 Abeta 沉积的机制最近受到了广泛的研究，可以通过几种不同的机制发生。重要的是，AD 患者的外周单核细胞似乎在清除 Abeta 方面存在缺陷。这篇综述将总结血液来源的细胞在 AD 中的作用的研究结果，并讨论它们在治疗患有这种毁灭性疾病的患者方面的治疗潜力。
