Viscoelastic and ultrastructural characteristics of whole blood and plasma in Alzheimer-type dementia, and the possible role of bacterial lipopolysaccharides (LPS).
Viscoelastic and ultrastructural characteristics of whole blood and plasma in Alzheimer-type dementia, and the possible role of bacterial lipopolysaccharides (LPS).
复制标题
阿尔茨海默氏型痴呆症中全血和血浆的粘弹性和超微结构特征，以及细菌脂多糖（LPS）的可能作用。
DOI：
10.18632/oncotarget.6074
复制
发表时间：
2015-11-03
期刊：
影响因子：
--
通讯作者：
Pretorius E
中科院分区：
文献类型：
--
作者：
Bester J;Soma P;Kell DB;Pretorius E
阿尔茨海默型痴呆（AD）是一种神经退行性疾病，也是最常见的痴呆形式。患者通常表现为神经系统和全身性炎症以及铁失调，与氧化损伤相关，反映在高凝状态中。高凝状态与纤维蛋白（原）增加密切相关，在AD患者中，纤维蛋白（原）与神经炎症和记忆缺陷的发展有关。仍然没有明确的原因，为什么（a）这种高凝状态，（B）铁失调和（c）增加的纤维蛋白（原）可以一起导致神经元结构和认知功能的丧失。在这里，我们提出了一个替代假设的基础上，以前的超微结构证据的存在（休眠）的血液微生物组在AD。此外，我们认为，细菌细胞壁成分，如革兰氏阴性菌株的内毒素脂多糖（LPS），可能是持续和低度炎症的原因，AD的特征。在这里，我们遵循一种综合方法，通过使用扫描电子显微镜、血栓弹力图（TEG®）和全球血栓形成试验（GTT®）研究AD血浆和全血的粘弹性和超微结构特性。超微结构分析证实了微生物的存在和红细胞的紧密接近。TEG®分析显示AD中的高凝状态。将LPS加入到初始血液中的TEG®结果显示出与AD患者相同的趋势，而GTT®结果（其中仅测量血小板活性）不受加入的LPS的影响，表明LPS不直接影响血小板功能。我们的研究结果加强了进一步研究LPS在AD中的作用的重要性。
Alzheimer-type dementia (AD) is a neurodegenerative disorder and the most common form of dementia. Patients typically present with neuro- and systemic inflammation and iron dysregulation, associated with oxidative damage that reflects in hypercoagulability. Hypercoagulability is closely associated with increased fibrin(ogen) and in AD patients fibrin(ogen) has been implicated in the development of neuroinflammation and memory deficits. There is still no clear reason precisely why (a) this hypercoagulable state, (b) iron dysregulation and (c) increased fibrin(ogen) could together lead to the loss of neuronal structure and cognitive function. Here we suggest an alternative hypothesis based on previous ultrastructural evidence of the presence of a (dormant) blood microbiome in AD. Furthermore, we argue that bacterial cell wall components, such as the endotoxin lipopolysaccharide (LPS) of Gram-negative strains, might be the cause of the continuing and low-grade inflammation, characteristic of AD. Here, we follow an integrated approach, by studying the viscoelastic and ultrastructural properties of AD plasma and whole blood by using scanning electron microscopy, Thromboelastography (TEG®) and the Global Thrombosis Test (GTT®). Ultrastructural analysis confirmed the presence and close proximity of microbes to erythrocytes. TEG® analysis showed a hypercoagulable state in AD. TEG® results where LPS was added to naive blood showed the same trends as were found with the AD patients, while the GTT® results (where only platelet activity is measured), were not affected by the added LPS, suggesting that LPS does not directly impact platelet function. Our findings reinforce the importance of further investigating the role of LPS in AD.