Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-β and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits

Zhi-Hao Liu ¹Yu-Di Bai ²Zhong-Yuan Yu ²Hui-Yun Li ²Jie Liu ²Cheng-Rong Tan ²Gui-Hua Zeng ²Yun-Feng Tu ²Pu-Yang Sun ²Yu-Juan Jia ²Jin-Cai He ³Yan-Jiang Wang ⁴Xian-Le Bu⁵

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作者信息

1. Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Neurology and Centre for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Chongqing Key Laboratory of Ageing and Brain Diseases,Chongqing 400042,China
2. Department of Neurology and Centre for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Chongqing Key Laboratory of Ageing and Brain Diseases,Chongqing 400042,China
3. Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China
4. Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Neurology and Centre for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Chongqing Key Laboratory of Ageing and Brain Diseases,Chongqing 400042,China;Institute of Brain and Intelligence,Third Military Medical University,Chongqing 400042,China;State Key Laboratory of Trauma,Burns and Combined Injury,Third Military Medical University,Chongqing 40
5. Department of Neurology and Centre for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China;Chongqing Key Laboratory of Ageing and Brain Diseases,Chongqing 400042,China;Institute of Brain and Intelligence,Third Military Medical University,Chongqing 400042,China;State Key Laboratory of Trauma,Burns and Combined Injury,Third Military Medical University,Chongqing 400042,China
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Abstract

Deficiencies in the clearance of peripheral amy-loid β(Aβ)play a crucial role in the progression of Alzhei-mer's disease(AD).Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD.However,the exact mechanism of Aβ clearance dys-function in AD monocytes remains unclear.In the present study,we found that blood monocytes in AD mice exhibited decreases in energy metabolism,which was accompanied by cellular senescence,a senescence-associated secretory phenotype,and dysfunctional phagocytosis of Aβ.Improv-ing energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro.Moreo-ver,enhancing blood monocyte Aβ phagocytosis by improv-ing energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive func-tion in AD mice.This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evi-dence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

Key words

Alzheimer's disease/Aβ clearance/Monocyte/Phagocytosis/Energy metabolism

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基金项目

National Natural Science Foundation of China(82122023)

National Natural Science Foundation of China(U22A20294)

出版年

2023

神经科学通报(英文版)

中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD

影响因子：0.741

ISSN：1673-7067

参考文献量51

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