Erythropoietin signaling in peripheral macrophages is required for systemic β‐amyloid clearance
Open accessAbstract
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.
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From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [330]
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- Authors
- Xu, L., Li, L., Pan, C., Song, J., Zhang, C., Wu, X., Hu, F., Liu, X., Zhang, Z., & Zhang, Z.
- Affiliations
- Nanjing Medical University (CN)
- State Key Laboratory of Reproductive Medicine (CN)
- Army Medical University (CN)
- Corresponding author
- Zhang, Zhiren
- Venue
- The EMBO Journal
- Published
- 2022-10-10
- Volume
- 41
- Issue
- 22
- Pages
- e111038-e111038
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC9670197
- OpenAlex
- W4304140851
- Cited by
- 29
- References
- 64
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 2 · 2023: 3
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82071209, 81771171, 82071778)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- erythropoietin, peripheral macrophages, amyloid-beta clearance, Alzheimer's disease, PPARγ, phagocytosis, EPO receptor, aging
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Erythropoietin, Macrophages, Mice, Transgenic, Amyloid beta-Peptides, Mice
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