| First Author | Chittimalli K | Year | 2024 |
| Journal | J Alzheimers Dis Rep | Volume | 8 |
| Issue | 1 | Pages | 981-998 |
| PubMed ID | 39114548 | Mgi Jnum | J:359204 |
| Mgi Id | MGI:7782772 | Doi | 10.3233/ADR-240024 |
| Citation | Chittimalli K, et al. (2024) An Investigation of the Inflammatory Landscape in the Brain and Bone Marrow of the APP/PS1 Mouse. J Alzheimers Dis Rep 8(1):981-998 |
| abstractText | BACKGROUND: The APP/PS1 mouse model recapitulates pathology of human Alzheimer's disease (AD). While amyloid-beta peptide deposition and neurodegeneration are features of AD, the pathology may involve inflammation and impaired vascular regeneration. OBJECTIVE: This study evaluated inflammatory environments in the brain and bone marrow (BM), and the impact on brain microvascular density. METHODS: BM and frontal cortex from male nine-month-old APP/PS1 or the control C57Bl6/j mice were studied. Vascular density and inflammatory cells were evaluated in the sections of frontal cortex by immunohistochemistry. Different subsets of hematopoietic stem/progenitor cells (BM) and monocyte-macrophages were characterized by flow cytometry and by clonogenic assays. Myelopoietic or inflammatory factors were evaluated by real-time RT-PCR or by western blotting. RESULTS: CD34(+) or CD31(+) vascular structures were lower (p < 0.01, n = 6) in the frontal cortex that was associated with decreased number of Lin(-)Sca-1(+)cKit(+) vasculogenic progenitor cells in the BM and circulation (p < 0.02, n = 6) compared to the control. Multipotent progenitor cells MPP4, common lymphoid, common myeloid and myeloid progenitor cells were higher in the APP/PS1-BM compared to the control, which agreed with increased numbers of monocytes and pro-inflammatory macrophages. The expression of pro-myelopoietic factors and alarmins was higher in the APP/PS1 BM-HSPCs or in the BM-supernatants compared to the control. Frontal cortices of APP/PS1 mice showed higher number of pro-inflammatory macrophages (CD11b(+)F4/80(+) or CD80(+)) and microglia (OX42(+)Iba1(+)). CONCLUSIONS: These findings show that AD pathology in APP/PS1 mice is associated with upregulated myelopoiesis, which contributes to the brain inflammation and decreased vascularity. |
