2. Academic Validation
  3. Erythropoietin signaling in peripheral macrophages is required for systemic β-amyloid clearance

Erythropoietin signaling in peripheral macrophages is required for systemic β-amyloid clearance

  • EMBO J. 2022 Oct 10;e111038. doi: 10.15252/embj.2022111038.
Lu Xu # 1 2 3,  Lei Li # 1,  Cai-Long Pan 1 2,  Jing-Jing Song 1,  Chen-Yang Zhang 1,  Xiang-Hui Wu 1,  Fan Hu 4,  Xue Liu 1,  Zhiren Zhang 5,  Zhi-Yuan Zhang 1 2 3 6
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
  • 2 Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China.
  • 3 Department of Neurology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
  • 4 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
  • 5 Institute of Immunology, Army Medical University, Chongqing, China.
  • 6 Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
  • # Contributed equally.
PMID: 36215698 DOI: 10.15252/embj.2022111038
Abstract

Impaired clearance of beta-amyloid (Aβ) is a primary cause of sporadic Alzheimer's disease (AD). Aβ clearance in the periphery contributes to reducing brain Aβ levels and preventing Alzheimer's disease pathogenesis. We show here that erythropoietin (EPO) increases phagocytic activity, levels of Aβ-degrading Enzymes, and Aβ clearance in peripheral macrophages via PPARγ. Erythropoietin is also shown to suppress Aβ-induced inflammatory responses. Deletion of EPO receptor in peripheral macrophages leads to increased peripheral and brain Aβ levels and exacerbates Alzheimer's-associated brain pathologies and behavioral deficits in AD-model mice. Moreover, erythropoietin signaling is impaired in peripheral macrophages of old AD-model mice. Exogenous erythropoietin normalizes impaired EPO signaling and dysregulated functions of peripheral macrophages in old AD-model mice, promotes systemic Aβ clearance, and alleviates disease progression. Erythropoietin treatment may represent a potential therapeutic approach for Alzheimer's disease.

Keywords

Alzheimer's disease; erythropoietin signaling; peripheral macrophages; systemic Aβ clearance.

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