{"doi":"10.3233/adr-240024","title":"An Investigation of the Inflammatory Landscape in the Brain and Bone Marrow of the APP/PS1 Mouse","abstract":"Background: The APP/PS1 mouse model recapitulates pathology of human Alzheimer’s disease (AD). While amyloid-β 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.","journal":"Journal of Alzheimer s Disease Reports","year":2024,"id":480476,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5887,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1320367,"name":"Stephen Adkins","orcid":null,"position":1,"is_corresponding":false},{"id":262558,"name":"Sanjay Arora","orcid":"0000-0002-7234-2398","position":2,"is_corresponding":false},{"id":262560,"name":"Jagdish Singh","orcid":"0000-0003-3198-2839","position":3,"is_corresponding":false},{"id":394562,"name":"Yagna Jarajapu","orcid":"0000-0002-7186-3693","position":4,"is_corresponding":false},{"id":419165,"name":"Kishore Chittimalli","orcid":null,"position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T02:07:02.142014Z","pmid":"39114548","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}