MINI REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1616939
The Role of Peripheral Innate Immune Cells in Alzheimer's Disease Progression
Provisionally accepted
- 1School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China., Lanzhou, Gansu Province, China
- 2Department of Neurology, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China., Lanzhou, Gansu Province, China
- 3The No.2 people’s hospital of Lanzhou, Lanzhou 730000, Gansu Province, China., Lanzhou, Gansu Province, China
- 4Xiaogan City social welfare and medical rehabilitation center, Xiaogan 432000, Hubei Province, China., Xiaogan, China
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, and chronic neuroinflammation. While microglia and astrocytes dominate CNS immune responses, emerging evidence implicates peripheral innate immune cells (PIICs)-including neutrophils, monocytes, dendritic cells, NK cells, and myeloid-derived suppressor cells (MDSCs)-as critical modulators of AD pathogenesis. This review synthesizes recent advances linking PIIC-related genetic polymorphisms to AD susceptibility and progression. We highlight how PIICs traffic into the brain via chemokine signaling, where they exhibit stage-specific effects: early recruitment may limit Aβ deposition via phagocytosis, whereas chronic infiltration exacerbates neuroinflammation and neuronal death. Paradoxically, some PIICs exert immunosuppressive effects that could be harnessed therapeutically. We further discuss preclinical strategies to modulate PIIC function, such as CCR2 inhibition, neutrophil depletion, and MDSC adoptive transfer. By bridging peripheral and central immunity, this review unveils PIICs as promising targets for next-generation AD therapies, advocating for precision immunomodulation tailored to disease stages.
Keywords: Alzheimer's disease, peripheral innate immunity, Neuroinflammation, trained immunity, Genetic polymorphisms, Myeloid-derived suppressor cells (MDSCs)
Received: 24 Apr 2025; Accepted: 01 Jul 2025.
Copyright: © 2025 Cao, Tang, Ma, Zhang, Yang, Li, Zhang and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoming Peng, Department of Neurology, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China., Lanzhou, Gansu Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.