The effects of high plasma levels of Aβ 1-42 on mononuclear macrophage in mouse models of Alzheimer’s disease

Microglia plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Plasma Aβ 1−42 levels significantly increased 15 years before the onset of dominantly inherited AD. The effects of high plasma levels of Aβ 1−42 on mononuclear macrophage, the peripheral counterparts of microglia, remains unclear. Herein, we used a parabiosis model to investigate the effects of plasma Aβ 1−42 on peripheral mononuclear macrophage and the possible mechanism. We found the proportions of pro-inflammatory macrophages in peritoneal cavity, myeloid derived suppressor cells (MDSCs) in spleen, granulocyte-monocyte progenitors (GMP) in bone marrow, and the plasma levels of interleukin-6 (IL-6) were significantly decreased after 4 months sustaining stimulation with high plasma levels of Aβ 1−42 . The proportions of pro-inflammatory macrophages, MDSCs, GMPs, the plasma levels of IL-6 and TNF-α, as well as the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased after 8 months sustaining stimulation with high plasma levels of Aβ 1−42 . In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were increased, however, the phagocytic function of macrophages had no obviously alteration after high plasma levels of Aβ 1−42 sustaining stimulation. These results demonstrated that high plasma levels of Aβ 1−42 had a biphasic regulating effects on the amounts of pro-inflammatory macrophages, MDSCs, and bone marrow myeloid progenitor cells, as well as the secretory function of macrophage. Herein, we suggest that the alterations of the amounts and proliferations of myeloid progenitor cells in bone marrow may be involved in the regulation of peripheral mononuclear macrophages and MDSCs, intervening the effects of plasma Aβ 1−42 on monocytes/macrophages might offer a new therapeutic approach to AD.