The article reviews the role of apolipoprotein E (apoE) and its receptors in Alzheimer's disease (AD). apoE, a major cholesterol carrier in the brain, is associated with a significant genetic risk for late-onset AD. The ε4 allele of the APOE gene, which codes for apoE4, is a strong risk factor for AD, contributing to disease pathogenesis by modulating amyloid-β (Aβ) metabolism and aggregation, and regulating brain lipid metabolism and synaptic functions through apoE receptors. The review highlights the biochemical properties of apoE and its isoforms, the structure and function of apoE receptors, and their roles in Aβ-dependent and Aβ-independent pathways. It discusses the potential therapeutic targets for AD, including disrupting apoE4 domain interaction, regulating apoE expression, and targeting apoE receptors. The article also explores the relationship between apoE and AD pathology, such as Aβ clearance, cholesterol homeostasis, synaptic plasticity, and neuronal toxicity. Finally, it emphasizes the need for further research to understand the complex interactions between apoE isoforms and receptors in AD pathogenesis and to develop effective therapies.The article reviews the role of apolipoprotein E (apoE) and its receptors in Alzheimer's disease (AD). apoE, a major cholesterol carrier in the brain, is associated with a significant genetic risk for late-onset AD. The ε4 allele of the APOE gene, which codes for apoE4, is a strong risk factor for AD, contributing to disease pathogenesis by modulating amyloid-β (Aβ) metabolism and aggregation, and regulating brain lipid metabolism and synaptic functions through apoE receptors. The review highlights the biochemical properties of apoE and its isoforms, the structure and function of apoE receptors, and their roles in Aβ-dependent and Aβ-independent pathways. It discusses the potential therapeutic targets for AD, including disrupting apoE4 domain interaction, regulating apoE expression, and targeting apoE receptors. The article also explores the relationship between apoE and AD pathology, such as Aβ clearance, cholesterol homeostasis, synaptic plasticity, and neuronal toxicity. Finally, it emphasizes the need for further research to understand the complex interactions between apoE isoforms and receptors in AD pathogenesis and to develop effective therapies.