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

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

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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.

Alzheimer's diseaseAβ clearanceMonocytePhagocytosisEnergy metabolism

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

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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

State Key Laboratory of Trauma,Burns and Combined Injury,Third Military Medical University,Chongqing 400042,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of China

82122023U22A20294

2023

10.1007/s12264-023-01077-y

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
年,卷(期)：2023.39(12)
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