Department of Anesthesia, Tinglin Hospital, Shanghai, China.
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Neurosci Lett. 2023 Mar 28;801:137159. doi: 10.1016/j.neulet.2023.137159. Epub 2023 Feb 27.
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Our previous study revealed that bone morphogenetic protein 9 (BMP9) could ameliorate the amyloid pathology and cognitive impairments in a transgenic model of AD. However, the mechanisms underlying the protective effect of BMP9 against amyloid pathology remain unknown. Low-density lipoprotein receptor-related protein 1 (LRP1) plays an essential role in the clearance of amyloid beta. Here, we demonstrated that intranasal BMP9 significantly enhanced the expression of LRP1 in the brains of APP/PS1 mice. Importantly, silencing LRP1 significantly promoted the amyloid plaques accumulation and facilitated the neuroinflammation in the brains of BMP9-treated APP/PS1 mice. Furthermore, silencing LRP1 significantly impaired the learning and memory functions of BMP9-treated APP/PS1 mice. Our results suggest that BMP9 ameliorate the amyloid pathology and cognitive dysfunction in APP/PS1 mice by promoting the expression of LRP1.
阿尔茨海默病（AD）是全球最常见的痴呆症病因。我们之前的研究表明，骨形态发生蛋白 9（BMP9）可以改善 AD 转基因模型中的淀粉样蛋白病理和认知障碍。然而，BMP9 对抗淀粉样蛋白病理的保护作用的机制尚不清楚。低密度脂蛋白受体相关蛋白 1（LRP1）在β淀粉样蛋白的清除中起着至关重要的作用。在这里，我们证明了鼻内 BMP9 显著增强了 APP/PS1 小鼠大脑中的 LRP1 表达。重要的是，沉默 LRP1 显著促进了 BMP9 处理的 APP/PS1 小鼠大脑中的淀粉样斑块积累和神经炎症。此外，沉默 LRP1 显著损害了 BMP9 处理的 APP/PS1 小鼠的学习和记忆功能。我们的研究结果表明，BMP9 通过促进 LRP1 的表达来改善 APP/PS1 小鼠的淀粉样蛋白病理和认知功能障碍。
