BMP9 ameliorates amyloid pathology by promoting low-density lipoprotein receptor-related protein 1 expression in APP/PS1 transgenic mice

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.