The association of the APOE4 (vs. APOE3) isoform with an increased risk of Alzheimer’s disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elucidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking the apolipoprotein isoform to disease etiology. The APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several changes in the pathways of lipid homeostasis in the brains of mice expressing the human APOE4 vs. APOE3 isoform. Carriers of APOE4 had altered cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing polyunsaturated fatty acids and an overall elevation in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related to increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of APOE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.
Emerging African countries are characterized by explosive population growth and urbanization, which threaten environmental sustainability. This study comparatively characterized ambient aerosols and assessed cytotoxicity to facilitate improving health and environmental policy. Twenty-four air samples were collected at high and low-density traffic sites in Kano State using polysulfone and stainless steel filters attached to an automated pump. The physico-chemical properties of particulate matter were determined using scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX). In vitro, their potential toxicity was assessed using macrophages and cell fixation with staining. Results showed 51.7% of particles as PM2.5, with the highest particle concentration in mixed sites (urban and industrial). Particle classification into four groups by elemental composition and structure showed: Si, Al, and Ca 58–67%; other fibres, Fe, S, Mo, and Zn 1–17%; non-sand non-fibres 23–56%; and silicone-based fibres 2–28%. The abundant elements are: Si, Al, Ca, Ce, Ti, Fe, Cl, Pb, and Mn. The lowest viability on cytotoxicity assessment was recorded in mixed site M2. The majority of households were located within 50 m of air sampling sites. Proximity to traffic sites worsens health, as evidenced in cytotoxicity findings. We recommend improved urban planning and intensification of emissions control.
Emerging African countries are characterized by explosive population growth and urbanization, which threaten environmental sustainability. This study comparatively characterized ambient aerosols and assessed cytotoxicity to facilitate improving health and environmental policy. Twenty-four air samples were collected at high and low-density traffic sites in Kano State using polysulfone and stainless steel filters attached to an automated pump. The physico-chemical properties of particulate matter were determined using scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX). In vitro, their potential toxicity was assessed using macrophages and cell fixation with staining. Results showed 51.7% of particles as PM2.5, with the highest particle concentration in mixed sites (urban and industrial). Particle classification into four groups by elemental composition and structure showed: sand particles (Si, Al, Fe, Ca, Mg, K, Na, Mo, Sr, Zr) 30–51%; other fibers 0–3%; other particles (Si, Fe, S, Mo, Zn, and other metals) 22–40%; and silicone-based fibres 23–34%. The abundant elements are: Si, Al, Ca, Ce, Ti, Fe, Cl, Pb, and Mn. The lowest viability on cytotoxicity assessment was recorded in mixed site M2. The majority of households were located within 50 m of air sampling sites. Proximity to traffic sites worsens health, as evidenced in cytotoxicity findings. We recommend improved urban planning and intensification of emissions control.
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