Iron Regulates Apolipoprotein E Expression and Secretion in Neurons and Astrocytes

Background: There is strong evidence that iron homeostasis is impaired in the aging and Alzheimer's disease (AD) brain and that this contributes to neurodegeneration. Apolipoprotein E (APOE) has been identified as the strongest genetic risk factor for AD. However, the interaction between the two has yet to be fully explored. Objective: This study aimed to investigate the relationship between exogenous iron levels and ApoE in neurons and astrocytes. Methods: Our study used primary cultured cortical neurons and astrocytes to investigate the changes in ApoE caused by iron. Western blot and RT-PCR were used to measure ApoE. Results: We observed that iron upregulated intracellular ApoE levels in both neurons and astrocytes at the post-transcriptional and transcriptional level, respectively. However, there was less full-length ApoE secreted by neurons and astrocytes after iron treatment. We speculate that this might impair brain lipid metabolism and amyloid-beta clearance. In terms of ApoE receptors, we observed that neuronal LRP-1 levels were increased by the addition of exogenous iron, which could contribute to A beta PP endocytosis in neurons. However, there were no significant changes in neuronal LDLR, astrocyte LDLR, or astrocyte LRP-1. Conclusion: Our study reveals that iron may contribute to the pathogenesis of AD by affecting ApoE and its receptors and supports the notion that iron chelation should be investigated as a therapeutic strategy for AD.