PMID- 37525137
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230803
IS  - 1742-4933 (Print)
IS  - 1742-4933 (Electronic)
IS  - 1742-4933 (Linking)
VI  - 20
IP  - 1
DP  - 2023 Jul 31
TI  - The effects of high plasma levels of Abeta(1-42) on mononuclear macrophage in mouse 
      models of Alzheimer's disease.
PG  - 39
LID - 10.1186/s12979-023-00366-4 [doi]
LID - 39
AB  - More and more evidences are proving that microglia play a crucial role in the 
      pathogenesis of Alzheimer's disease (AD) and the plasma Abeta(1-42) levels 
      significantly increased 15 years before the onset of dominantly inherited AD. 
      However, the effects of high plasma levels of Abeta(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 Abeta(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)-alpha, 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 
      Abeta(1-42) sustaining stimulation. These results demonstrated that high plasma 
      levels of Abeta(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 Abeta(1-42) on pro-inflammatory macrophages might offer a new 
      therapeutic approach to AD.
CI  - (c) 2023. The Author(s).
FAU - Li, Chunrong
AU  - Li C
AD  - Department of Neurology, Neuroscience Center, The First Hospital of Jilin 
      University, Jilin University, Changchun, 130021, China.
AD  - Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital 
      of Shenzhen University, Shenzhen, 518055, China.
FAU - Liu, Kangding
AU  - Liu K
AD  - Department of Neurology, Neuroscience Center, The First Hospital of Jilin 
      University, Jilin University, Changchun, 130021, China.
FAU - Zhu, Jie
AU  - Zhu J
AD  - Department of Neurology, Neuroscience Center, The First Hospital of Jilin 
      University, Jilin University, Changchun, 130021, China.
AD  - Department of Neurobiology, Care Sciences & Society, Division of Neurogeriatrics, 
      Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
FAU - Zhu, Feiqi
AU  - Zhu F
AD  - Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital 
      of Shenzhen University, Shenzhen, 518055, China. zfqzsu2004@aliyun.com.
LA  - eng
GR  - SZSM201801014/Sanming Project of Medicine in Shenzhen City/
GR  - JCYJ20200109143431341/Key project of Shenzhen Science and Technology Innovation 
      Committee/
PT  - Journal Article
DEP - 20230731
PL  - England
TA  - Immun Ageing
JT  - Immunity & ageing : I & A
JID - 101235427
PMC - PMC10388532
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Abeta1-42
OT  - Bone marrow myeloid progenitor cells
OT  - Mononuclear macrophage
OT  - Myeloid derived suppressor cells
COIS- The authors declare no competing interests.
EDAT- 2023/08/01 01:08
MHDA- 2023/08/01 01:09
PMCR- 2023/07/31
CRDT- 2023/07/31 23:38
PHST- 2022/11/30 00:00 [received]
PHST- 2023/07/18 00:00 [accepted]
PHST- 2023/08/01 01:09 [medline]
PHST- 2023/08/01 01:08 [pubmed]
PHST- 2023/07/31 23:38 [entrez]
PHST- 2023/07/31 00:00 [pmc-release]
AID - 10.1186/s12979-023-00366-4 [pii]
AID - 366 [pii]
AID - 10.1186/s12979-023-00366-4 [doi]
PST - epublish
SO  - Immun Ageing. 2023 Jul 31;20(1):39. doi: 10.1186/s12979-023-00366-4.