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However, the effects of high plasma levels of A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    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 A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    on peripheral mononuclear macrophage. Our results showed that in the early stage of Tg mice (7\u00a0months) and Pa (Wt-Tg) mice (4\u00a0months), 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)-\u03b1, as well as\u00a0the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased in the late stage of Tg mice (11\u00a0months) and Pa (Wt-Tg) mice (8\u00a0months). In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were enhanced consistently, and the phagocytic function of\u00a0macrophages kept stably after high plasma levels of A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    \u00a0sustaining stimulation. These results demonstrated that high plasma levels of A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    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 A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    on pro-inflammatory macrophages might offer a new therapeutic approach to AD.\n                  <\/jats:p>","DOI":"10.1186\/s12979-023-00366-4","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T03:02:35Z","timestamp":1690772555000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The effects of high plasma levels of A\u03b21-42 on mononuclear macrophage in mouse models of Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"20","author":[{"given":"Chunrong","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kangding","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiqi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"issue":"10284","key":"366_CR1","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","volume":"397","author":"P Scheltens","year":"2021","unstructured":"Scheltens P, De Strooper B, Kivipelto M, et al. 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