An Investigation of the Inflammatory Landscape in the Brain and Bone Marrow of the APP/PS1 Mouse.

Background: The APP/PS1 mouse model recapitulates pathology of human Alzheimer's disease (AD). While amyloid-ß 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.

The Chickahominy T.R.U.T.H. (Trust, Research, Understand, Teach, and Heal) Project-A Tribal Community-Academic Partnership for Understanding the Impact of Structural Factors on Perceived Cancer Risk in Rural Virginia.

In 2022, the Virginia Chickahominy Indian Tribe partnered with Virginia Commonwealth University Massey Comprehensive Cancer Center to investigate concerns about a potential cancer cluster near a local landfill. While investigating cancer clusters is complex due to long latency and multifactorial causes, the community's concerns about structural factors driving cancer risk warrant exploration. Thus, the Chickahominy T.R.U.T.H. (Trust, Research, Understand, Teach, and Heal) Project was created as a community-academic partnership to (1) identify structural factors and barriers associated with perceived cancer risk and care; (2) assess cancer knowledge, care access gaps, and perceived risks, including testing private and community water sources; (3) develop and deploy culturally tailored cancer education and resource navigation, including groundwater safety education, policies, and remediation. We will conduct 150 in-person interviews and water tests among residents within a four-mile radius of the landfill, and deploy 1000 structured questionnaires among Charles City County residents. In this paper, we provide an overview of the ongoing project design, development, and progress in support of the project's objectives. This collaborative investigation aims to address cancer health disparities, enhance research and health policy advocacy, and honor the sacred knowledge of an underserved community, laying the groundwork for a long-term partnership to guide future research questions.