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- W3197453178 abstract "Abstract Background : Microglia play a crucial role in the pathogenesis of Alzheimer’s disease (AD). Plasma Aβ 1-42 levels significantly increase 15 years before the onset of dominantly inherited AD. The effects of high plasma levels of Aβ 1-42 on monocytes and macrophages, the hematogenous counterparts of microglia, remain unclear. Methods : We investigated the effects of plasma Aβ 1-42 on peripheral monocytes and macrophages in three animal models, including 7- and 11-month-old female APPswe/PS1dE9 (APP/PS1) transgenic (Tg) mice, wild-type (Wt) parabiotic with Tg (paWt(Wt-Tg)) mice, and Wt mice. Results : We found that high plasma levels of Aβ 1-42 , in younger (7-month) AD mice significantly decreased the amounts of pro-inflammatory macrophages, myeloid derived suppressor cells (MDSCs), granulocyte-monocyte progenitors (GMP), and the plasma levels of interleukin-6 (IL-6). In older (11-month) AD mice, high plasma levels of Aβ 1-42 significantly increased the amounts of pro-inflammatory macrophages, MDSCs, GMPs, the plasma levels of IL-6 and TNF-α, and the brain infiltration of bone marrow-derived macrophages (BMDMs). However, high plasma levels of Aβ 1-42 consistently increased the amounts of monocytes and the proliferation of bone marrow cells (BMCs) without affecting the phagocytic function of macrophages on Aβ 1-42 . Conclusion : The response of mouse AD model suggests that a high plasma level of Aβ 1-42 affects monocytes and macrophages via its biphasic effects on MDSCs and GMPs. We suggest that intervening in the effects of plasma Aβ 1-42 on monocytes and macrophages might offer a new therapeutic approach to AD." @default.
- W3197453178 created "2021-09-13" @default.
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- W3197453178 date "2021-09-01" @default.
- W3197453178 modified "2023-10-02" @default.
- W3197453178 title "High Plasma Levels of Aβ1-42 Affect Monocytes and Macrophages via Biphasic Effects on Myeloid-Derived Suppressor Cells and Granulocyte-Monocyte Progenitors in Mouse Models of Alzheimer’s Disease" @default.
- W3197453178 doi "https://doi.org/10.21203/rs.3.rs-789627/v1" @default.
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