Pretorius Etheresia, Bester Janette, Page Martin J, Kell Douglas B
Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Front Aging Neurosci. 2018 Aug 22;10:257. doi: 10.3389/fnagi.2018.00257. eCollection 2018.
Many studies indicate that there is a (mainly dormant) microbial component in the progressive development of Alzheimer-type dementias (ADs); and that in the case of Gram-negative organisms, a chief culprit might be the shedding of the highly inflammagenic lipopolysaccharide (LPS) from their cell walls. We have recently shown that a highly sensitive assay for the presence of free LPS [added to platelet poor plasma (PPP)] lies in its ability (in healthy individuals) to induce blood to clot into an amyloid form. This may be observed in a SEM or in a confocal microscope when suitable amyloid stains (such as thioflavin T) are added. This process could be inhibited by human lipopolysaccharide-binding protein (LBP). In the current paper, we show using scanning electron microscopy and confocal microscopy with amyloid markers, that PPP taken from individuals with AD exhibits considerable amyloid structure when clotting is initiated with thrombin but without added LPS. Furthermore, we could show that this amyloid structure may be reversed by the addition of very small amounts of LBP. This provides further evidence for a role of microbes and their inflammagenic cell wall products and that these products may be involved in pathological clotting in individuals with AD.
许多研究表明，在阿尔茨海默型痴呆症（AD）的渐进发展过程中存在一种（主要处于休眠状态的）微生物成分；对于革兰氏阴性菌而言，一个主要的罪魁祸首可能是其细胞壁上具有高度炎症性的脂多糖（LPS）脱落。我们最近发现，一种用于检测游离LPS（添加到乏血小板血浆（PPP）中）存在的高灵敏度检测方法，在于其（在健康个体中）能够诱导血液凝结成淀粉样形式的能力。当添加合适的淀粉样染色剂（如硫黄素T）时，在扫描电子显微镜或共聚焦显微镜下可以观察到这种情况。这个过程可以被人脂多糖结合蛋白（LBP）抑制。在本文中，我们使用扫描电子显微镜和带有淀粉样标记物的共聚焦显微镜表明，从AD患者身上采集的PPP在使用凝血酶启动凝血但未添加LPS时，会呈现出相当多的淀粉样结构。此外，我们可以证明，添加极少量的LBP可以使这种淀粉样结构逆转。这为微生物及其具有炎症性的细胞壁产物的作用提供了进一步的证据，并且这些产物可能参与了AD患者的病理性凝血过程。
