The effects of high plasma levels of Aβ1-42 on mononuclear macrophage in mouse models of Alzheimer's disease

Chunrong Li; Kangding Liu; Jie Zhu; Feiqi Zhu

doi:10.1186/s12979-023-00366-4

The effects of high plasma levels of Aβ_1-42 on mononuclear macrophage in mouse models of Alzheimer's disease

Immun Ageing. 2023 Jul 31;20(1):39. doi: 10.1186/s12979-023-00366-4.

Authors

Chunrong Li^{1

2}, Kangding Liu¹, Jie Zhu^{1

3}, Feiqi Zhu⁴

Affiliations

¹ Department of Neurology, Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, 130021, China.
² Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518055, China.
³ Department of Neurobiology, Care Sciences & Society, Division of Neurogeriatrics, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
⁴ Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518055, China. zfqzsu2004@aliyun.com.

Abstract

More and more evidences are proving that microglia play a crucial role in the pathogenesis of Alzheimer's disease (AD) and the plasma Aβ_1-42 levels significantly increased 15 years before the onset of dominantly inherited AD. However, the effects of high plasma levels of Aβ_1-42 on mononuclear macrophage, the peripheral counterparts of microglia, remain unclear. In the present study, we used APP/PS1 transgenic (Tg) mice and a parabiotic model of wild type (Wt) mice and Tg mice (Parabiotic Wt-Tg, Pa (Wt-Tg)) to investigate the effects of high plasma levels of Aβ_1-42 on peripheral mononuclear macrophage. Our results showed that in the early stage of Tg mice (7 months) and Pa (Wt-Tg) mice (4 months), the proportions of pro-inflammatory macrophages in peritoneal cavity, myeloid derived suppressor cells (MDSCs) in spleen, granulocyte-monocyte progenitors (GMPs) in bone marrow, and the plasma levels of interleukin-6 (IL-6) were significantly decreased. While the proportions of pro-inflammatory macrophages, MDSCs, GMPs, and the plasma levels of IL-6 and tumor necrosis factor (TNF)-α, as well as the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased in the late stage of Tg mice (11 months) and Pa (Wt-Tg) mice (8 months). In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were enhanced consistently, and the phagocytic function of macrophages kept stably after high plasma levels of Aβ_1-42 sustaining stimulation. These results demonstrated that high plasma levels of Aβ_1-42 play a biphasic regulating role at different stages of the disease, namely inhibiting effects on peripheral pro-inflammatory macrophages in the early stage of AD model, while promoting effects in the late stage of AD model. The mechanism behind this may be associated with their effects on MDSCs in spleen and myeloid progenitor cells in bone marrow. Therefore, intervening the effects of plasma Aβ_1-42 on pro-inflammatory macrophages might offer a new therapeutic approach to AD.

Keywords: Alzheimer’s disease; Aβ1-42; Bone marrow myeloid progenitor cells; Mononuclear macrophage; Myeloid derived suppressor cells.

Abstract

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