Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
Institute of Brain and Intelligence, Third Military Medical University, Chongqing, China.
Aging Cell. 2022 Jan;21(1):e13533. doi: 10.1111/acel.13533. Epub 2021 Dec 23.
A previous study demonstrated that nearly 40%-60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aβ in the periphery.
We investigated the physiological clearance of Aβ by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice.
We found that Aβ levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aβ is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aβ directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aβ burden and AD-related pathologies in AD mice.
Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aβ in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.
先前的研究表明，近 40%-60%的大脑 Aβ 流出到外周系统进行清除。然而，循环 Aβ 在周围环境中是如何被清除的仍不清楚。脾脏是血液过滤器和免疫器官。本研究旨在探讨脾脏在清除外周 Aβ 中的作用。
我们通过脾脏研究了 Aβ 的生理清除，并通过切除 APP/PS1 小鼠的脾脏建立了 AD 小鼠模型，以研究脾切除对 AD 小鼠的影响。
我们发现脾动脉中的 Aβ 水平高于脾静脉，表明当血液流经脾脏时，循环中的 Aβ 被清除。接下来，我们发现脾脏单核细胞/巨噬细胞可以在体内和体外直接摄取 Aβ。脾切除加重了 AD 小鼠的行为缺陷、脑 Aβ 负荷和 AD 相关病理。
本研究首次揭示了脾脏在外周发挥清除循环 Aβ 的生理功能。我们的研究还表明，脾切除术是治疗脾破裂和脾功能亢进的常规疗法，可能会加速 AD 的发展。
