Department of Public Health, Experimental Medicine & Forensic, University of Pavia, Pavia, Italy.
J Alzheimers Dis. 2014;39(1):169-79. doi: 10.3233/JAD-131394.
Data found in literature have reported that bacterial endotoxins may be involved in the inflammatory and pathological processes associated with amyloidosis and Alzheimer's disease (AD). In fact, it has been observed that the chronic infusion of the bacterial lipopolysaccharide, the outer cell wall component of Gram negative bacteria, into the fourth ventricle of rats reproduces many of the inflammatory and pathological features seen in the brain of AD patients. In this context, a key player in the pathogenesis of AD is the amyloid-β peptide (Aβ) that is capable of aggregating in fibrils that represent the main component of amyloid plaques. These deposits that accumulate among brain cells are indeed one of the hallmarks of AD. This aggregation in fibrils seems to correlate with Aβ toxic effects. However, recent data have shown that amyloid fibril formation not only results in toxic aggregates but also provides biologically functional molecules; such amyloids have been identified on the surface of fungi and bacteria. The aim of this work was to gain insight into the influence of bacterial endotoxins on Aβ fibrillogenesis; factors that influence fibril formation may be important for Aβ toxic potential. Following three days of incubation at 37°C, Aβ was organized in compact fibrils and the in vitro Aβ fibrillogenesis was potentiated by the Escherichia coli endotoxin. This suggests the importance of infectious events in the pathogenesis of AD and proposes a new aspect related to the putative pathological factors that can be implicated in the mechanisms involved in Aβ25-35 fibrillogenesis.
文献中的数据表明，细菌内毒素可能与淀粉样变性和阿尔茨海默病（AD）相关的炎症和病理过程有关。事实上，已经观察到革兰氏阴性菌的外细胞壁成分细菌脂多糖的慢性输注到大鼠的第四脑室中，可再现 AD 患者大脑中所见的许多炎症和病理特征。在这种情况下，AD 发病机制中的关键参与者是淀粉样β肽（Aβ），它能够聚集在纤维中，纤维是淀粉样斑块的主要成分。这些在脑细胞之间积累的沉积物确实是 AD 的标志之一。这种纤维状聚集似乎与 Aβ 的毒性作用相关。然而，最近的数据表明，纤维状淀粉样蛋白的形成不仅导致有毒聚集体，而且还提供具有生物学功能的分子；在真菌和细菌的表面已经鉴定出这种淀粉样蛋白。这项工作的目的是深入了解细菌内毒素对 Aβ 纤维形成的影响；影响纤维形成的因素对于 Aβ 的毒性潜力可能很重要。在 37°C 孵育三天后，Aβ被组织成紧密的纤维，并且大肠杆菌内毒素增强了体外 Aβ纤维形成。这表明感染事件在 AD 的发病机制中的重要性，并提出了一个与假定的病理因素相关的新方面，这些因素可能与 Aβ25-35 纤维形成的机制有关。
