阿尔茨海默病（AD）是一种随年龄而发展的神经系统疾病。据推测，淀粉样蛋白-β（Aβ）聚集可能是阿尔茨海默病的关键发病过程。从人参(Panax ginseng C.A. Meyer)中分离出的人参多糖(Ginseng polysaccharides, GP)是主要的活性成分，可能作为神经保护剂对阿尔茨海默病患者有潜在的益处。然而，GP对Aβ病理和AD症状的影响仍不清楚。本研究中，我们纯化了一种名为GP4的4.7-kDa GP，并对其进行了基本的物理化学表征。然后，我们使用跨物种AD模型评估了GP4预防Aβ聚集的生物学效果，包括经Aftin-5处理的SH-SY5Y细胞和脑器官样体以及过表达全长人源性Aβ42肽的转基因秀丽隐杆线虫。这些分析最终表明，GP4能够在体内和体外抑制Aβ的积累，并且早期干预GP4足以减轻秀丽隐杆线虫AD模型中与Aβ42相关的衰老表型和记忆损失。此外，神经炎症在人类细胞和脑器官样体中明显下调。从机制学角度来看，我们发现GP4抑制Aβ聚集的能力与其促进神经元线粒体自噬活性有关。这一发现为进一步开发GP4作为治疗AD候选药物提供了坚实的理论基础。版权所有 © 2023. Elsevier Masson SAS出版。

Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-β (Aβ) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer (ginseng), may act as neuroprotective agents with potential benefits for AD patients. However, GP effects on Aβ pathology and AD symptoms are still unclear. Here, a 4.7-kDa GP termed GP4 was purified and subjected to basic physicochemical characterization. The biological effects of GP4 to prevent Aβ aggregation were then assessed with cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ42 peptide. These analyses ultimately demonstrated that GP4 was capable of inhibiting Aβ accumulation both in vivo and vitro, and with early intervention of GP4 being sufficient to alleviate Aβ42-associated aging phenotypes and memory loss in C. elegans model of AD. Furthermore, neuroinflammation was significantly down-regulated in human cells and cerebral organoids. From a mechanistic perspective, the ability of GP4 to inhibit Aβ aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD.Copyright © 2023. Published by Elsevier Masson SAS.