The amyloid-beta (Aβ) fibrillation process seems to execute a principal role in the neuropathology of Alzheimer's disease (AD). Accordingly, novel therapeutic plans have concentrated on the inhibition or degradation of Aβ oligomers and fibrils. Biocompatible nanoparticles (NPs), e.g., gold and iron oxide NPs, take a unique capacity in redirecting Aβ fibrillation kinetics; nevertheless, their impacts on AD-related memory impairment have not been adequately evaluated in vivo. Here, we examined the effect of commercial PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) on the learning and memory of an AD-animal model. The outcomes demonstrated the dose-dependent effect of SPIONs on Aβ fibrillation and learning and memory processes. In vitro and in vivo findings revealed that Low doses of SPIONs inhibited Aβ aggregation and ameliorated learning and memory deficit in the AD model, respectively. Enhanced level of hippocampal proteins, including brain-derived neurotrophic factor, BDNF, phosphorylated-cAMP response element-binding protein, p-CREB, and stromal interaction molecules, e.g., STIM1 and STIM2, were also observed. However, at high doses, SPIONs did not improve the detrimental impacts of Aβ fibrillation on spatial memory and hippocampal proteins expression. Overall, we revealed the potential capacity of SPIONs on retrieval of behavioral and molecular manifestations of AD in vivo, which needs further investigations to determine the mechanistic effect of SPIONs in the AD conundrum.

淀粉样蛋白-β (Aβ) 纤颤过程似乎在阿尔茨海默病 (AD) 的神经病理学中起主要作用。因此，新的治疗计划集中在 Aβ 寡聚体和原纤维的抑制或降解上。生物相容性纳米粒子 (NPs)，例如金和氧化铁 NPs，在重定向 Aβ 纤颤动力学方面具有独特的能力；然而，它们对 AD 相关记忆障碍的影响尚未在体内得到充分评估。在这里，我们研究了商业 PEG 化超顺磁性氧化铁纳米粒子 (SPION) 对 AD 动物模型的学习和记忆的影响。结果证明了 SPIONs 对 Aβ 纤颤以及学习和记忆过程的剂量依赖性影响。体外和体内研究结果表明，低剂量的 SPIONs 分别抑制了 AD 模型中的 Aβ 聚集并改善了学习和记忆缺陷。还观察到海马蛋白水平提高，包括脑源性神经营养因子、BDNF、磷酸化 cAMP 反应元件结合蛋白、p-CREB ​​和基质相互作用分子，例如STIM1 和 STIM2。然而，在高剂量下，SPIONs 并没有改善 Aβ 纤颤对空间记忆和海马蛋白表达的不利影响。总体而言，我们揭示了 SPIONs在体内检索 AD 行为和分子表现的潜在能力，这需要进一步研究以确定 SPIONs 在 AD 难题中的机制作用。