文献类型：期刊文献

英文题名：The Synergistic Role of ApoE4 and GSK3β in Alzheimer's Disease: Pathological Mechanisms and Therapeutic Implications

作者：Li, Qianwei[1];Shang, Yinghui[1];Huang, Han-Chang[1];Dai, Xueling[1];Lao, Fengxue[1,2]

第一作者：Li, Qianwei

通讯作者：Lao, FX[1];Lao, FX[2]

机构：[1]Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China;[2]Beijing Union Univ, Coll Appl Sci & Technol, Beijing 100012, Peoples R China

第一机构：北京联合大学生物化学工程学院

通讯机构：[1]corresponding author), Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China;[2]corresponding author), Beijing Union Univ, Coll Appl Sci & Technol, Beijing 100012, Peoples R China.|[1141775]北京联合大学应用科技学院;[11417]北京联合大学;[1141726]北京联合大学生物化学工程学院;

年份：2025

卷号：63

期号：1

外文期刊名：MOLECULAR NEUROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001613381500002)】；

基金：This study was supported by the Academic Research Projects of Beijing Union University (ZKZD202304 and ZK70202101).

语种：英文

外文关键词：Alzheimer's disease; GSK3 beta; ApoE4; PI3K/AKT; Wnt/beta-catenin; Lipid metabolism

摘要：Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by significant cognitive decline. Glycogen synthase kinase-3 beta (GSK3 beta), a key regulator in the pathological process of AD, exacerbates neuronal damage by phosphorylating tau proteins and promoting A beta production. The activity of GSK3 beta is modulated by multiple signaling cascades, including the PI3K/AKT and Wnt/beta-catenin transduction pathways. Furthermore, Apolipoprotein E epsilon 4 (ApoE4) has been identified as a major genetic risk factor for increased susceptibility to AD. ApoE4 aggravates lipid metabolism disorders by interfering with LRP1 receptor function, inhibiting insulin signaling, and promoting the release of inflammatory factors (IL-6, TNF-alpha) and GSK3 beta. Specifically, ApoE4 may intensify the pathological process of AD by interacting with GSK3 beta, altering the balance of lipid metabolism in the body, regulating GSK3 beta activity, and modulating neuroinflammatory responses. This article systematically reviews the synergistic mechanisms of ApoE4 and GSK3 beta in AD and provides a new theoretical basis and potential intervention strategies for early diagnosis and targeted therapy of AD.