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  3. 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

  • Neurosci Bull. 2023 Jun 15. doi: 10.1007/s12264-023-01077-y.
Zhi-Hao Liu 1 2 3,  Yu-Di Bai 2 3,  Zhong-Yuan Yu 2 3,  Hui-Yun Li 2 3,  Jie Liu 2 3,  Cheng-Rong Tan 2 3,  Gui-Hua Zeng 2 3,  Yun-Feng Tu 2 3,  Pu-Yang Sun 2 3,  Yu-Juan Jia 2 3,  Jin-Cai He 4,  Yan-Jiang Wang 5 6 7 8 9 10,  Xian-Le Bu 11 12 13 14
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 2 Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
  • 3 Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.
  • 4 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. hjc@wmu.edu.cn.
  • 5 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. yanjiang_wang@tmmu.edu.cn.
  • 6 Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. yanjiang_wang@tmmu.edu.cn.
  • 7 Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China. yanjiang_wang@tmmu.edu.cn.
  • 8 Institute of Brain and Intelligence, Third Military Medical University, Chongqing, 400042, China. yanjiang_wang@tmmu.edu.cn.
  • 9 State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400042, China. yanjiang_wang@tmmu.edu.cn.
  • 10 Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 201200, China. yanjiang_wang@tmmu.edu.cn.
  • 11 Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. buxianle@sina.cn.
  • 12 Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China. buxianle@sina.cn.
  • 13 Institute of Brain and Intelligence, Third Military Medical University, Chongqing, 400042, China. buxianle@sina.cn.
  • 14 State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400042, China. buxianle@sina.cn.
PMID: 37316674 DOI: 10.1007/s12264-023-01077-y
Abstract

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer'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 dysfunction 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. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

Keywords

Alzheimer’s disease; Aβ clearance; Energy metabolism; Monocyte; Phagocytosis.

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