The Role of APOE4 in Regulating LRP1 on Aβ<sub>25-35</sub>-Induced Oxidative Stress and Inflammatory Response in Astrocytes

Yanping LI; Efty Fariha Tasnim; Zhixing LU; Lingying ZHU

doi:10.12259/j.issn.2095-610X.S20251103

Volume 46 Issue 11

Nov. 2025

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Yanping LI, Efty Fariha Tasnim, Zhixing LU, Lingying ZHU. The Role of APOE4 in Regulating LRP1 on Aβ25-35-Induced Oxidative Stress and Inflammatory Response in Astrocytes[J]. Journal of Kunming Medical University, 2025, 46(11): 18-25. doi: 10.12259/j.issn.2095-610X.S20251103

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Yanping LI, Efty Fariha Tasnim, Zhixing LU, Lingying ZHU. The Role of APOE4 in Regulating LRP1 on Aβ_25-35-Induced Oxidative Stress and Inflammatory Response in Astrocytes[J]. Journal of Kunming Medical University, 2025, 46(11): 18-25. doi: 10.12259/j.issn.2095-610X.S20251103

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The Role of APOE4 in Regulating LRP1 on Aβ_25-35-Induced Oxidative Stress and Inflammatory Response in Astrocytes

doi: 10.12259/j.issn.2095-610X.S20251103

1.
Department of Neurology，Yan’An Hospital Affiliated to Kunming Medical University，Kunming Yunnan 650051
2.
Yunnan Yunke Biotechnology Research Institute Kunming Yunnan 650224，China

Received Date: 2025-07-29
Publish Date: 2025-11-25

Abstract

Abstract

Objective To investigate the effect of APOE4 in regulating LRP1 and on β-amyloid protein Aβ_25-35-induced oxidative stress and inflammatory response in astrocytes. Methods Human astrocytes were transfected with sh-NC, sh-APOE4, pcDNA-NC, and pcDNA-LRP1, and then induced with 10 μM Aβ_25-35 for 24 h to establish an AD cell model. The roles of APOE4 and LRP1 in Aβ_25-35-induced oxidative stress and inflammatory response were assessed using Western blot, flow cytometry, the detection kits of MDA, SOD, and GSH, as well as enzyme-linked immunosorbent assay （ELISA） kits for TNF-α, IL-6, and IL-1β. The protein-protein interaction between APOE4 and LRP1 was detected through co-immunoprecipitation and western blot experiments. Results Aβ_25-35 induction upregulated APOE4 expression （P < 0.01）, promoted the levels of ROS （ P < 0.001）, MDA （ P < 0.001）, and inflammatory cytokines TNF-α, IL-6, and IL-1β （ P < 0.001） in astrocytes, while inhibited the expression of SOD, GSH, and LRP1 （ P < 0.001）. Knockdown of APOE4 or overexpression of LRP1 suppressed the Aβ _25-35-induced increase in ROS, oxidative stress markers, and inflammatory cytokines in cells （P < 0.05）. APOE4 negatively regulated LRP1 protein expression through protein-protein interactions. The levels of ROS, MDA, and inflammatory cytokines were higher （ P < 0.05）, and the concentrations of SOD and GSH were lower （ P < 0.001）, in cells with simultaneous knockdown of APOE4 and LRP1 compared to those with APOE4 knockdown alone. Conclusion Knockdown of APOE4 attenuates Aβ_25-35-induced oxidative stress and inflammatory response in astrocytes by upregulating LRP1.
- Alzheimer's disease,
- Astrocytes,
- Oxidative stress,
- Inflammatory response

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References(28)

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